WorldWideScience

Sample records for structure variations peptide

  1. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery....... To better understand the underlying mechanisms of antibody-antigen interaction here we present a pipeline developed by us to structurally classify immunoglobulin antigen binding sites and to infer key sequence residues and other variables that have a prominent role in each structural class....

  2. Variation, structure and norms

    DEFF Research Database (Denmark)

    Harder, Peter

    2014-01-01

    in linguistics: those that see linguistic norms as antithetical to a descriptive and variational linguistics. Once such a re-evaluation has taken place, however, the social recontextualization of cognition will enable linguistics (including sociolinguistics as an integral part), to eliminate the cracks...... that an evolutionary account can reintegrate the opposed fragments into a whole picture that puts each of them in their ‘ecological position’ with respect to each other. Empirical usage facts should be seen in the context of operational norms in relation to which actual linguistic choices represent adaptations....... Variational patterns should be seen in the context of structural categories without which there would be only ‘differences’ rather than variation. And emergence, individual choice, and flux should be seen in the context of the individual’s dependence on lineages of community practice sustained by collective...

  3. Structural Interplay - Tuning Mechanics in Peptide-Polyurea Hybrids

    Science.gov (United States)

    Korley, Lashanda

    Utilizing cues from natural materials, we have been inspired to explore the hierarchical arrangement critical to energy absorption and mechanical enhancement in synthetic systems. Of particular interest is the soft domain ordering proposed as a contributing element to the observed toughness in spider silk. Multiblock copolymers, are ideal and dynamic systems in which to explore this approach via variations in secondary structure of nature's building blocks - peptides. We have designed a new class of polyurea hybrids that incorporate peptidic copolymers as the soft segment. The impact of hierarchical ordering on the thermal, mechanical, and morphological behavior of these bio-inspired polyurethanes with a siloxane-based, peptide soft segment was investigated. These peptide-polyurethane/urea hybrids were microphase segregated, and the beta-sheet secondary structure of the soft segment was preserved during polymerization and film casting. Toughness enhancement at low strains was achieved, but the overall extensibility of the peptide-incorporated systems was reduced due to the unique hard domain organization. To decouple the secondary structure influence in the siloxane-peptide soft segment from mechanics dominated by the hard domain, we also developed non-chain extended peptide-polyurea hybrids in which the secondary structure (beta sheet vs. alpha helix) was tuned via choice of peptide and peptide length. It was shown that this structural approach allowed tailoring of extensibility, toughness, and modulus. The sheet-dominant hybrid materials were typically tougher and more elastic due to intermolecular H-bonding facilitating load distribution, while the helical-prevalent systems generally exhibited higher stiffness. Recently, we have explored the impact of a molecular design strategy that overlays a covalent and physically crosslinked architecture in these peptide-polyurea hybrids, demonstrating that physical constraints in the network hybrids influences peptide

  4. Structural pattern matching of nonribosomal peptides

    Directory of Open Access Journals (Sweden)

    Leclère Valérie

    2009-03-01

    Full Text Available Abstract Background Nonribosomal peptides (NRPs, bioactive secondary metabolites produced by many microorganisms, show a broad range of important biological activities (e.g. antibiotics, immunosuppressants, antitumor agents. NRPs are mainly composed of amino acids but their primary structure is not always linear and can contain cycles or branchings. Furthermore, there are several hundred different monomers that can be incorporated into NRPs. The NORINE database, the first resource entirely dedicated to NRPs, currently stores more than 700 NRPs annotated with their monomeric peptide structure encoded by undirected labeled graphs. This opens a way to a systematic analysis of structural patterns occurring in NRPs. Such studies can investigate the functional role of some monomeric chains, or analyse NRPs that have been computationally predicted from the synthetase protein sequence. A basic operation in such analyses is the search for a given structural pattern in the database. Results We developed an efficient method that allows for a quick search for a structural pattern in the NORINE database. The method identifies all peptides containing a pattern substructure of a given size. This amounts to solving a variant of the maximum common subgraph problem on pattern and peptide graphs, which is done by computing cliques in an appropriate compatibility graph. Conclusion The method has been incorporated into the NORINE database, available at http://bioinfo.lifl.fr/norine. Less than one second is needed to search for a pattern in the entire database.

  5. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik

    2014-01-01

    peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides...... and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic pepti-domimetics that refine peptide structure and confer biological properties....

  6. Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition

    KAUST Repository

    Chan, Kiat Hwa

    2017-10-04

    Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven amino acids, for which our laboratory has found many biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucine-leucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications.

  7. StraPep: a structure database of bioactive peptides

    Science.gov (United States)

    Wang, Jian; Yin, Tailang; Xiao, Xuwen; He, Dan; Xue, Zhidong; Jiang, Xinnong; Wang, Yan

    2018-01-01

    Abstract Bioactive peptides, with a variety of biological activities and wide distribution in nature, have attracted great research interest in biological and medical fields, especially in pharmaceutical industry. The structural information of bioactive peptide is important for the development of peptide-based drugs. Many databases have been developed cataloguing bioactive peptides. However, to our knowledge, database dedicated to collect all the bioactive peptides with known structure is not available yet. Thus, we developed StraPep, a structure database of bioactive peptides. StraPep holds 3791 bioactive peptide structures, which belong to 1312 unique bioactive peptide sequences. About 905 out of 1312 (68%) bioactive peptides in StraPep contain disulfide bonds, which is significantly higher than that (21%) of PDB. Interestingly, 150 out of 616 (24%) bioactive peptides with three or more disulfide bonds form a structural motif known as cystine knot, which confers considerable structural stability on proteins and is an attractive scaffold for drug design. Detailed information of each peptide, including the experimental structure, the location of disulfide bonds, secondary structure, classification, post-translational modification and so on, has been provided. A wide range of user-friendly tools, such as browsing, sequence and structure-based searching and so on, has been incorporated into StraPep. We hope that this database will be helpful for the research community. Database URL: http://isyslab.info/StraPep PMID:29688386

  8. Unusual structural transition of antimicrobial VP1 peptide.

    Science.gov (United States)

    Shanmugam, Ganesh; Phambu, Nsoki; Polavarapu, Prasad L

    2011-05-01

    VP1 peptide, an active domain of m-calpain enzyme with antimicrobial activity is found to undergo an unusual conformational transition in trifluoroethanol (TFE) solvent. The nature of, and time dependent variations in, circular dichroism associated with the amide I vibrations, suggest that VP1 undergoes self-aggregation forming anti-parallel β-sheet structure in TFE. Transmission electron micrograph (TEM) images revealed that β-sheet aggregates formed by VP1 possess fibril-like assemblies. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Structure variations of carbonizing lignin

    International Nuclear Information System (INIS)

    Otani, C.; Polidoro, H.A.; Otani, S.; Craievich, A.F.

    1984-01-01

    The studied lignin is a by-product of the process of ethanol production from eucaliptus. It was heat-treated under inert atmosphere conditions at increasing temperatures from 300C up to 2400C. The structural variations were studied by wide-angle X-ray diffraction, small-angle X-ray scattering and infrared absorption spectroscopy. The bulk and 'real' density of the compacted materials have also been determined as functions of the final temperature. These experimental results enabled us to establish a mechanism of structure variation based on the formation of a turbostratic graphite-like and porous structure within the initially amorphous lignin matrix. (Author) [pt

  10. Structural basis of nonribosomal peptide macrocyclization in fungi.

    Science.gov (United States)

    Zhang, Jinru; Liu, Nicholas; Cacho, Ralph A; Gong, Zhou; Liu, Zhu; Qin, Wenming; Tang, Chun; Tang, Yi; Zhou, Jiahai

    2016-12-01

    Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (C T ) domain and the holo thiolation (T)-C T complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.

  11. Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function

    KAUST Repository

    Rydberg, Hanna A.

    2012-10-01

    Cell-penetrating peptides and antimicrobial peptides are two classes of positively charged membrane active peptides with several properties in common. The challenge is to combine knowledge about the membrane interaction mechanisms and structural properties of the two classes to design peptides with membrane-specific actions, useful either as transporters of cargo or as antibacterial substances. Membrane active peptides are commonly rich in arginine and tryptophan. We have previously designed a series of arg/trp peptides and investigated how the position and number of tryptophans affect cellular uptake. Here we explore the antimicrobial properties and the interaction with lipid model membranes of these peptides, using minimal inhibitory concentrations assay (MIC), circular dichroism (CD) and linear dichroism (LD). The results show that the arg/trp peptides inhibit the growth of the two gram positive strains Staphylococcus aureus and Staphylococcus pyogenes, with some individual variations depending on the position of the tryptophans. No inhibition of the gram negative strains Proteus mirabilis or Pseudomonas aeruginosa was noticed. CD indicated that when bound to lipid vesicles one of the peptides forms an α-helical like structure, whereas the other five exhibited rather random coiled structures. LD indicated that all six peptides were somehow aligned parallel with the membrane surface. Our results do not reveal any obvious connection between membrane interaction and antimicrobial effect for the studied peptides. By contrast cell-penetrating properties can be coupled to both the secondary structure and the degree of order of the peptides. © 2012 Elsevier Inc.

  12. Aggregation and toxicity of amyloid-beta peptide in relation to peptide sequence variation

    OpenAIRE

    Vandersteen, A.

    2012-01-01

    Generally, aggregation of the amyloid-ß peptide is considered the cause of neuronal death in Alzheimer disease. The heterogenous Aß peptide occurs in various lengths in vivo: Aß40 and Aß42 are the predominant forms while both shorter and longer peptides exist. Aß40 and shorter isoforms are less aggregation-prone and hence considered less dangerous than Aß42 and longer isoforms, which are more aggregation-prone. Up to now research mainly focussed on the predominant Aß peptides and their indivi...

  13. Structural basis for precursor protein-directed ribosomal peptide macrocyclization

    Science.gov (United States)

    Li, Kunhua; Condurso, Heather L.; Li, Gengnan; Ding, Yousong; Bruner, Steven D.

    2016-01-01

    Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides whose members target proteases with potent reversible inhibition. The product structure is constructed by three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here, we describe the detailed structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases, MdnC and MdnB, interact with a conserved α-helix of the precursor peptide using a novel precursor peptide recognition mechanism. The results provide insight into the unique protein/protein interactions key to the chemistry, suggest an origin of the natural combinatorial synthesis of microviridin peptides and provide a framework for future engineering efforts to generate designed compounds. PMID:27669417

  14. Structural basis for precursor protein-directed ribosomal peptide macrocyclization.

    Science.gov (United States)

    Li, Kunhua; Condurso, Heather L; Li, Gengnan; Ding, Yousong; Bruner, Steven D

    2016-11-01

    Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved α-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight into the unique protein-protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.

  15. Variational identities and Hamiltonian structures

    International Nuclear Information System (INIS)

    Ma Wenxiu

    2010-01-01

    This report is concerned with Hamiltonian structures of classical and super soliton hierarchies. In the classical case, basic tools are variational identities associated with continuous and discrete matrix spectral problems, targeted to soliton equations derived from zero curvature equations over general Lie algebras, both semisimple and non-semisimple. In the super case, a supertrace identity is presented for constructing Hamiltonian structures of super soliton equations associated with Lie superalgebras. We illustrate the general theories by the KdV hierarchy, the Volterra lattice hierarchy, the super AKNS hierarchy, and two hierarchies of dark KdV equations and dark Volterra lattices. The resulting Hamiltonian structures show the commutativity of each hierarchy discussed and thus the existence of infinitely many commuting symmetries and conservation laws.

  16. Structure-activity relationship of CART peptide fragments

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Hlaváček, Jan; Blokešová, Darja; Elbert, Tomáš; Šanda, Miloslav; Slaninová, Jiřina; Železná, Blanka

    2007-01-01

    Roč. 88, č. 4 (2007), s. 565 ISSN 0006-3525. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : cocaine and amphetamine regulated transcript peptide * structure * activity Subject RIV: CE - Biochemistry

  17. Maturation processes and structures of small secreted peptides in plants

    Directory of Open Access Journals (Sweden)

    Ryo eTabata

    2014-07-01

    Full Text Available In the past decade, small secreted peptides have proven to be essential for various aspects of plant growth and development, including the maintenance of certain stem cell populations. Most small secreted peptides identified in plants to date are recognised by membrane-localized receptor kinases, the largest family of receptor proteins in the plant genome. This peptide-receptor interaction is essential for initiating intracellular signalling cascades. Small secreted peptides often undergo post-translational modifications and proteolytic processing to generate the mature peptides. Recent studies suggest that, in contrast to the situation in mammals, the proteolytic processing of plant peptides involves a number of complex steps. Furthermore, NMR-based structural analysis demonstrated that post-translational modifications induce the conformational changes needed for full activity. In this mini review, we summarise recent advances in our understanding of how small secreted peptides are modified and processed into biologically active peptides and describe the mature structures of small secreted peptides in plants.

  18. Primary structure and conformational analysis of peptide methionine-tyrosine, a peptide related to neuropeptide Y and peptide YY isolated from lamprey intestine

    DEFF Research Database (Denmark)

    Conlon, J M; Bjørnholm, B; Jørgensen, Flemming Steen

    1991-01-01

    A peptide belonging to the pancreatic-polypeptide-fold family of regulatory peptides has been isolated from the intestine of an Agnathan, the sea lamprey (Petromyzon marinus). The primary structure of the peptide (termed peptide methionine-tyrosine) was established as Met-Pro-Pro-Lys-Pro-Asp-Asn-...... in a preferred structure in which the conformation of the beta-turn between the two helical domains (residues 9-14) is appreciably different....

  19. Electrostatic Force Microscopy of Self Assembled Peptide Structures

    DEFF Research Database (Denmark)

    Clausen, Casper Hyttel; Dimaki, Maria; Pantagos, Spyros P.

    2011-01-01

    In this report electrostatic force microscopy (EFM) is used to study different peptide self-assembled structures, such as tubes and particles. It is shown that not only geometrical information can be obtained using EFM, but also information about the composition of different structures. In partic......In this report electrostatic force microscopy (EFM) is used to study different peptide self-assembled structures, such as tubes and particles. It is shown that not only geometrical information can be obtained using EFM, but also information about the composition of different structures...

  20. Structure-activity relationship of crustacean peptide hormones.

    Science.gov (United States)

    Katayama, Hidekazu

    2016-01-01

    In crustaceans, various physiological events, such as molting, vitellogenesis, and sex differentiation, are regulated by peptide hormones. To understanding the functional sites of these hormones, many structure-activity relationship (SAR) studies have been published. In this review, the author focuses the SAR of crustacean hyperglycemic hormone-family peptides and androgenic gland hormone and describes the detailed results of our and other research groups. The future perspectives will be also discussed.

  1. Disulfide Bridges: Bringing Together Frustrated Structure in a Bioactive Peptide.

    Science.gov (United States)

    Zhang, Yi; Schulten, Klaus; Gruebele, Martin; Bansal, Paramjit S; Wilson, David; Daly, Norelle L

    2016-04-26

    Disulfide bridges are commonly found covalent bonds that are usually believed to maintain structural stability of proteins. Here, we investigate the influence of disulfide bridges on protein dynamics through molecular dynamics simulations on the cysteine-rich trypsin inhibitor MCoTI-II with three disulfide bridges. Correlation analysis of the reduced cyclic peptide shows that two of the three disulfide distances (Cys(11)-Cys(23) and Cys(17)-Cys(29)) are anticorrelated within ∼1 μs of bridge formation or dissolution: when the peptide is in nativelike structures and one of the distances shortens to allow bond formation, the other tends to lengthen. Simulations over longer timescales, when the denatured state is less structured, do not show the anticorrelation. We propose that the native state contains structural elements that frustrate one another's folding, and that the two bridges are critical for snapping the frustrated native structure into place. In contrast, the Cys(4)-Cys(21) bridge is predicted to form together with either of the other two bridges. Indeed, experimental chromatography and nuclear magnetic resonance data show that an engineered peptide with the Cys(4)-Cys(21) bridge deleted can still fold into its near-native structure even in its noncyclic form, confirming the lesser role of the Cys(4)-Cys(21) bridge. The results highlight the importance of disulfide bridges in a small bioactive peptide to bring together frustrated structure in addition to maintaining protein structural stability. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Structures and related properties of helical, disulfide-stabilized peptides

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, Mark D. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1993-11-01

    The three dimensional structure of several peptides were determined by NMR spectroscopy and distance geometry calculations. Each peptide formed a predictable, rigid structure, consisting of an α-helix, a "scaffold" region which packed along one face of the helix, and two disulfide bridges which covalently connect the helix and scaffold regions. The peptide Apa-M5 was designed to constrain the M5 peptide from MLCK in a helical geometry using the apamin disulfide scaffold. This scaffold constrains the N- terminal end of the helix with two disulfide bridges and a reverse turn. Like the M5 peptide, Apa-M5 was found to bind calmodulin in a Ca2+-dependent 1:1 stoichiometry. However, the dissociation constant of the (Apa-M5)-calmodulin complex, 107 nM, was 100-fold higher than the dissociation constant of the M5-calmodulin complex. This difference was due to a putative steric overlap between the Apa-M5 scaffold and calmodulin. The peptide Apa-Cro was designed to replace the large structural protein matrix of λ Cro with the apamin disulfide scaffold. However, Apa-Cro did not bind the consensus DNA operator half-site of λ Cro, probably due to a steric overlap between the Apa-Cro disulfide framework and the DNA. The amino acid sequence of the scaffold-disulfide bridge arrangement of the peptide Max was derived from the core sequence of scyllatoxin, which contains an α-helix constrained at the C-terminal end by two disulfide bridges and a two-stranded βsheet scaffold. Max was shown to fold with >84% yield to form a predictable, stable structure that is similar to scyllatoxin. The folding and stability properties of Max make this scaffold and disulfide bridge arrangement an ideal candidate for the development of hybrid sequence peptides. The dynamics of a fraying C-terminal end of the helix of the peptide Apa-AlaN was determined by analysis of 15N NMR relaxation properties.

  3. Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition

    KAUST Repository

    Chan, Kiat Hwa; Xue, Bo; Robinson, Robert C.; Hauser, Charlotte

    2017-01-01

    Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven

  4. Interplay between Peptide Bond Geometrical Parameters in Nonglobular Structural Contexts

    Directory of Open Access Journals (Sweden)

    Luciana Esposito

    2013-01-01

    Full Text Available Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides. Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-Cα-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-Cα-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability.

  5. Interplay between peptide bond geometrical parameters in nonglobular structural contexts.

    Science.gov (United States)

    Esposito, Luciana; Balasco, Nicole; De Simone, Alfonso; Berisio, Rita; Vitagliano, Luigi

    2013-01-01

    Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides). Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-C(α)-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-C(α)-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability.

  6. Structure variations of pumpkin balloon

    Science.gov (United States)

    Yajima, N.; Izutsu, N.; Honda, H.

    2004-01-01

    A lobed pumpkin balloon by 3-D gore design concept is recognized as a basic form for a super-pressure balloon. This paper deals with extensions of this design concept for other large pressurized membrane structures, such as a stratospheric airship and a balloon of which volume is controllable. The structural modifications are performed by means of additional ropes, belts or a strut. When the original pumpkin shape is modified by these systems, the superior characteristics of the 3-D gore design, incorporating large bulges with a small local radius and unidirectional film tension, should be maintained. Improved design methods which are adequate for the above subjects will be discussed in detail. Application for ground structures are also mentioned.

  7. Structural Basis for Degenerate Recognition of Natural HIV Peptide Variants by Cytotoxic Lymphocytes

    International Nuclear Information System (INIS)

    Martinez-Hackert, E.; Anikeeva, N.; Kalams, S.; Walker, B.; Hendrickson, W.; Sykulev, Y.

    2006-01-01

    It is well established that even small changes in amino acid side chains of antigenic peptide bound to MHC protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T-cell receptor (TCR). Often, however, several non-conservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the HIV p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes (CTL), which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein, and we have used synthetic variants to explore the wider spectrum of recognition. High-resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR, and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals

  8. Genetic Variation in the Natriuretic Peptide System, Circulating Natriuretic Peptide Levels, and Blood Pressure

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen L; Nielsen, Søren J; Torp-Pedersen, Christian

    2012-01-01

    -h ambulatory BP measurements (ABPMs) will influence the effect of NP gene variations on BP levels.MethodsWe used rs632793 at the NPPB (NP precursor B) locus to investigate the relationship between genetically determined serum N-terminal pro-brain NP (NT-proBNP) concentrations and BP levels...... determined by both 24-h ABPMs and OBPMs in a population consisting of 1,397 generally healthy individuals taking no BP-lowering drugs.Resultsrs632793 was significantly correlated with serum Nt-proBNP levels (r = 0.10, P = 0.0003), and participants with the A:A genotype had lower serum Nt-proBNP levels than......). Office BP decreased across the genotypes from A:A to G:G, but the differences did not reach statistical significance (P = 0.12).ConclusionsThis study suggests that 24-h ABPMs is a better method than OBPMs to detect significant differences in BP levels related to genetic variance and provides further...

  9. Recognition of GPCRs by peptide ligands and membrane compartments theory: structural studies of endogenous peptide hormones in membrane environment.

    Science.gov (United States)

    Sankararamakrishnan, Ramasubbu

    2006-04-01

    One of the largest family of cell surface proteins, G-protein coupled receptors (GPCRs) regulate virtually all known physiological processes in mammals. With seven transmembrane segments, they respond to diverse range of extracellular stimuli and represent a major class of drug targets. Peptidergic GPCRs use endogenous peptides as ligands. To understand the mechanism of GPCR activation and rational drug design, knowledge of three-dimensional structure of receptor-ligand complex is important. The endogenous peptide hormones are often short, flexible and completely disordered in aqueous solution. According to "Membrane Compartments Theory", the flexible peptide binds to the membrane in the first step before it recognizes its receptor and the membrane-induced conformation is postulated to bind to the receptor in the second step. Structures of several peptide hormones have been determined in membrane-mimetic medium. In these studies, micelles, reverse micelles and bicelles have been used to mimic the cell membrane environment. Recently, conformations of two peptide hormones have also been studied in receptor-bound form. Membrane environment induces stable secondary structures in flexible peptide ligands and membrane-induced peptide structures have been correlated with their bioactivity. Results of site-directed mutagenesis, spectroscopy and other experimental studies along with the conformations determined in membrane medium have been used to interpret the role of individual residues in the peptide ligand. Structural differences of membrane-bound peptides that belong to the same family but differ in selectivity are likely to explain the mechanism of receptor selectivity and specificity of the ligands. Knowledge of peptide 3D structures in membrane environment has potential applications in rational drug design.

  10. Interplay between Peptide Bond Geometrical Parameters in Nonglobular Structural Contexts

    OpenAIRE

    Esposito, Luciana; Balasco, Nicole; De Simone, Alfonso; Berisio, Rita; Vitagliano, Luigi

    2013-01-01

    Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (am...

  11. RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential

    Science.gov (United States)

    Findeisen, Maria; Rathmann, Daniel; Beck-Sickinger, Annette G.

    2011-01-01

    Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists) to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family. Furthermore, we address the biological functions of the ligands and give an overview on their involvement in physiological processes. We provide insights in the knowledge for the design of highly selective ligands for single receptor subtypes to minimize cross-talk and to eliminate effects from interactions within the GPCR system. This will support the drug development of members of the RFamide family.

  12. RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential

    Directory of Open Access Journals (Sweden)

    Maria Findeisen

    2011-09-01

    Full Text Available Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family. Furthermore, we address the biological functions of the ligands and give an overview on their involvement in physiological processes. We provide insights in the knowledge for the design of highly selective ligands for single receptor subtypes to minimize cross-talk and to eliminate effects from interactions within the GPCR system. This will support the drug development of members of the RFamide family.

  13. Structural Basis of Rap Phosphatase Inhibition by Phr Peptides

    Science.gov (United States)

    Gallego del Sol, Francisca; Marina, Alberto

    2013-01-01

    Two-component systems, composed of a sensor histidine kinase and an effector response regulator (RR), are the main signal transduction devices in bacteria. In Bacillus, the Rap protein family modulates complex signaling processes mediated by two-component systems, such as competence, sporulation, or biofilm formation, by inhibiting the RR components involved in these pathways. Despite the high degree of sequence homology, Rap proteins exert their activity by two completely different mechanisms of action: inducing RR dephosphorylation or blocking RR binding to its target promoter. However the regulatory mechanism involving Rap proteins is even more complex since Rap activity is antagonized by specific signaling peptides (Phr) through a mechanism that remains unknown at the molecular level. Using X-ray analyses, we determined the structure of RapF, the anti-activator of competence RR ComA, alone and in complex with its regulatory peptide PhrF. The structural and functional data presented herein reveal that peptide PhrF blocks the RapF-ComA interaction through an allosteric mechanism. PhrF accommodates in the C-terminal tetratricopeptide repeat domain of RapF by inducing its constriction, a conformational change propagated by a pronounced rotation to the N-terminal ComA-binding domain. This movement partially disrupts the ComA binding site by triggering the ComA disassociation, whose interaction with RapF is also sterically impaired in the PhrF-induced conformation of RapF. Sequence analyses of the Rap proteins, guided by the RapF-PhrF structure, unveil the molecular basis of Phr recognition and discrimination, allowing us to relax the Phr specificity of RapF by a single residue change. PMID:23526880

  14. Antimicrobial peptides: the role of hydrophobicity in the alpha helical structure

    Directory of Open Access Journals (Sweden)

    Pandurangan Perumal

    2013-12-01

    Full Text Available The antimicrobial peptides (AMPs are a class of molecule obtained from plants, insects, animals, and humans. These peptides have been classified into five categories: 1. Anionic peptide, 2. Linear alpha helical cationic peptide, 3. Cationic peptide, 4. Anionic and cationic peptides with disulphide bonds, and 5. Anionic and cationic peptide fragments of larger proteins. Factors affecting AMPs are sequence, size, charge, hydrophobicity, amphipathicity, structure and conformation. Synthesis of these peptides is convenient by using solid phase peptide synthesis by using FMOC chemistry protocol. The secondary structures of three synthetic peptides were determined by circular dichroism. Also, it was compared the stability of the α-helical structure and confirmed the percentage of helix of these peptides by using circular dichroism. Some of these AMPs show therapeutic properties like antimicrobial, antiviral, contraceptive, and anticancer. The formulations of some peptides have been entered into the phase I, II, or III of clinical trials. This article to review briefly the sources, classification, factors affecting AMPs activity, synthesis, characterization, mechanism of action and therapeutic concern of AMPs and mainly focussed on percentage of α-helical structure in various medium.

  15. The leader peptide of mutacin 1140 has distinct structural components compared to related class I lantibiotics.

    Science.gov (United States)

    Escano, Jerome; Stauffer, Byron; Brennan, Jacob; Bullock, Monica; Smith, Leif

    2014-12-01

    Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that promotes the core peptide's interaction with the post translational modification (PTM) enzymes. Following PTMs, mutacin 1140 is transported out of the cell and the leader peptide is cleaved to yield the antibacterial peptide. Mutacin 1140 leader peptide is structurally unique compared to other class I lantibiotic leader peptides. Herein, we further our understanding of the structural differences of mutacin 1140 leader peptide with regard to other class I leader peptides. We have determined that the length of the leader peptide is important for the biosynthesis of mutacin 1140. We have also determined that mutacin 1140 leader peptide contains a novel four amino acid motif compared to related lantibiotics. PTM enzyme recognition of the leader peptide appears to be evolutionarily distinct from related class I lantibiotics. Our study on mutacin 1140 leader peptide provides a basis for future studies aimed at understanding its interaction with the PTM enzymes. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Structural genomic variations and Parkinson's disease.

    Science.gov (United States)

    Bandrés-Ciga, Sara; Ruz, Clara; Barrero, Francisco J; Escamilla-Sevilla, Francisco; Pelegrina, Javier; Vives, Francisco; Duran, Raquel

    2017-10-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030. Until about 20 years ago, PD was considered to be the textbook example of a "non-genetic" disorder. Nowadays, PD is generally considered a multifactorial disorder that arises from the combination and complex interaction of genes and environmental factors. To date, a total of 7 genes including SNCA, LRRK2, PARK2, DJ-1, PINK 1, VPS35 and ATP13A2 have been seen to cause unequivocally Mendelian PD. Also, variants with incomplete penetrance in the genes LRRK2 and GBA are considered to be strong risk factors for PD worldwide. Although genetic studies have provided valuable insights into the pathogenic mechanisms underlying PD, the role of structural variation in PD has been understudied in comparison with other genomic variations. Structural genomic variations might substantially account for such genetic substrates yet to be discovered. The present review aims to provide an overview of the structural genomic variants implicated in the pathogenesis of PD.

  17. I-Ad-binding peptides derived from unrelated protein antigens share a common structural motif

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Colon, S

    1988-01-01

    on the I-Ad binding of the immunogenic peptide OVA 323-339. The results obtained demonstrated the very permissive nature of Ag-Ia interaction. We also showed that unrelated peptides that are good I-Ad binders share a common structural motif and speculated that recognition of such motifs could represent...... that I-Ad molecules recognize a large library of Ag by virtue of common structural motifs present in peptides derived from phylogenetically unrelated proteins....

  18. Applications of Circular Dichroism for Structural Analysis of Gelatin and Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Yoonkyung Park

    2012-03-01

    Full Text Available Circular dichroism (CD is a useful technique for monitoring changes in the conformation of antimicrobial peptides or gelatin. In this study, interactions between cationic peptides and gelatin were observed without affecting the triple helical content of the gelatin, which was more strongly affected by anionic surfactant. The peptides did not adopt a secondary structure in the presence of aqueous solution or Tween 80, but a peptide secondary structure formed upon the addition of sodium dodecyl sulfate (SDS. The peptides bound to the phosphate group of lipopolysaccharide (LPS and displayed an alpha-helical conformation while (KW4 adopted a folded conformation. Further, the peptides did not specifically interact with the fungal cell wall components of mannan or laminarin. Tryptophan blue shift assay indicated that these peptides interacted with SDS, LPS, and gelatin but not with Tween 80, mannan, or laminarin. The peptides also displayed antibacterial activity against P. aeruginosa without cytotoxicity against HaCaT cells at MIC, except for HPA3NT3-analog peptide. In this study, we used a CD spectroscopic method to demonstrate the feasibility of peptide characterization in numerous environments. The CD method can thus be used as a screening method of gelatin-peptide interactions for use in wound healing applications.

  19. Tuning peptide amphiphile supramolecular structure for biomedical applications

    Science.gov (United States)

    Pashuck, Eugene Thomas, III

    The use of biomaterials in regenerative medicine has been an active area of research for more than a decade. Peptide amphiphiles, which are short peptide sequences coupled to alkyl tails, have been studied in the Stupp group since the beginning of the decade and been used for a variety of biomedical applications. Most of the work has focused on the bioactive epitopes places on the periphery of the PA molecules, but the interior amino acids, known as the beta-sheet region, give the PA nanofiber gel much of its mechanical strength. To study the important parameters in the beta-sheet region, six PA molecules were constructed to determine the influence of beta-sheet length and order of the amino acids in the beta-sheet. It was found that having beta-sheet forming amino acids near the center of the fiber improves PA gel stiffness, and that having extra amino acids that have preferences for other secondary structures, like alpha-helix decreased the gels stiffness. Using FTIR and circular dichroism it was found that the mechanical properties are influenced by the amount of twist in the beta-sheet, and PAs that have more twisted beta-sheets form weaker gels. The effect amino acid properties have on peptide amphiphile self-assembly where studied by synthesizining molecules with varying side group size and hydrophobicity. It was found that smaller amino acids lead to stiffer gels and when two amino acids had the same size the amino acid with the larger beta-sheet propensity lead to a stiffer gel. Furthermore, small changes in peptide structure were found to lead to big changes in nanostructure, as leucine and isoleucine, which have the same size but slightly different structures, form flat ribbons and cylindrical nanofibers, respectively. Phenylalanine and alanine were studied more indepth because they represent the effects of adding an aromatic group to amino acids in the beta-sheet regon. These phenylalanine PAs formed short, twisted ribbons when freshly dissolved in water

  20. Structural requirements for the interaction between class II MHC molecules and peptide antigens

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Appella, E

    1990-01-01

    of binding, it is possible to define certain structural features of peptides that are associated with the capacity to bind to a particular MHC specificity (IA(d) or IE(d)); 3) IA(d) and IE(d) molecules recognize different and independent structures on the antigen molecule; 4) only about 10% of the single...... IA(d) and IE(d) molecules and their peptide ligands, we found that some structural characteristics apply to both antigen-MHC interactions. In particular, we found: 1) each MHC molecule is capable of binding many unrelated peptides through the same peptide-binding site; 2) despite this permissiveness...... amino acid substitutions tested on two IA(d)- and IE(d)-binding peptides had significant effect on their MHC-binding capacities, while over 80% of these substitutions significantly impaired T cell recognition of the Ia-peptide complex; 5) based on the segregation between residues that are crucial for T...

  1. Distribution and seasonal variation in hypothalamic RF-amide peptides in a semi-desert rodent, the jerboa

    DEFF Research Database (Denmark)

    Janati, A; Talbi, R; Klosen, P

    2013-01-01

    , kisspeptin (Kp) and RF-amide-related peptide (RFRP)-3, displays seasonal variation in jerboa. Kp and/or RFRP-3 immunoreactivity was investigated in the hypothalamus of jerboas captured in the field of the Middle Atlas mountain (Morocco), either in the spring or autumn. As in other rodents, the Kp...

  2. The effects of variations in dose and method of administration on glucagon like peptide-2 activity in the rat

    DEFF Research Database (Denmark)

    Kaji, Tatsuru; Tanaka, Hiroaki; Holst, Jens Juul

    2008-01-01

    Glucagon-like peptide-2 (GLP-2) is a potent, intestinal-specific trophic hormone. However, the relationship between the dose and timing of GLP-2 administration and these trophic effects is not clear. We investigated the effects of variations in the dose and timing of GLP-2 administration on its...

  3. Multi-structure docking analysis of BACE1 crystal structures and non-peptidic ligands.

    Science.gov (United States)

    Haghighijoo, Zahra; Hemmateenejad, Bahram; Edraki, Najmeh; Miri, Ramin; Emami, Saeed

    2017-09-01

    In order to design novel non-peptidic inhibitors of BACE1, many research groups have attempted using computational studies including docking analyses. Since there are too many 3D structures for BACE1 in the protein database, the selection of suitable crystal structures is a key prerequisite for the successful application of molecular docking. We employed a multi-structure docking protocol. In which 615 ligands' structures were docked into 150 BACE1 structures. The large number of the resultant docking scores were post-processed by different data analysis methods including exploratory data analysis, regression analysis and discriminant analysis. It was found that using one crystal structure for docking did not result in high accuracy for predicting activity of the BACE1 inhibitors. Instead, using of the multi-structural docking scores, post-processed by chemometrics methods arrived to highly accurate predictive models. In this regards, the PDB accession codes of 4B70, 4DVF and 2WEZ could discriminate between active and inactive compounds, with higher accuracy. Clustering of the BACE1 structures based on principal component analysis of the crystallographic structures the revealed that the discriminant structures are in the center of the clusters. Thus, these structures can be selected as predominant crystal structures for docking studies of non-peptidic BACE1 inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Elucidation of Peptide-Directed Palladium Surface Structure for Biologically Tunable Nanocatalysts

    Energy Technology Data Exchange (ETDEWEB)

    Bedford, Nicholas M.; Ramezani-Dakhel, Hadi; Slocik, Joseph M.; Briggs, Beverly D.; Ren, Yang; Frenkel, Anatoly I.; Petkov, Valeri; Heinz, Hendrik; Naik, Rajesh R.; Knecht, Mark R.

    2015-05-01

    Peptide-enabled synthesis of inorganic nanostructures represents an avenue to access catalytic materials with tunable and optimized properties. This is achieved via peptide complexity and programmability that is missing in traditional ligands for catalytic nanomaterials. Unfortunately, there is limited information available to correlate peptide sequence to particle structure and catalytic activity to date. As such, the application of peptide-enabled nanocatalysts remains limited to trial and error approaches. In this paper, a hybrid experimental and computational approach is introduced to systematically elucidate biomolecule-dependent structure/function relationships for peptide-capped Pd nanocatalysts. Synchrotron X-ray techniques were used to uncover substantial particle surface structural disorder, which was dependent upon the amino acid sequence of the peptide capping ligand. Nanocatalyst configurations were then determined directly from experimental data using reverse Monte Carlo methods and further refined using molecular dynamics simulation, obtaining thermodynamically stable peptide-Pd nanoparticle configurations. Sequence-dependent catalytic property differences for C-C coupling and olefin hydrogenation were then eluddated by identification of the catalytic active sites at the atomic level and quantitative prediction of relative reaction rates. This hybrid methodology provides a clear route to determine peptide-dependent structure/function relationships, enabling the generation of guidelines for catalyst design through rational tailoring of peptide sequences

  5. Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

    Science.gov (United States)

    Soliman, Wael; Wang, Liru; Bhattacharjee, Subir; Kaur, Kamaljit

    2011-04-14

    Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.

  6. Structural prediction and analysis of VIH-related peptides from selected crustacean species.

    Science.gov (United States)

    Nagaraju, Ganji Purna Chandra; Kumari, Nunna Siva; Prasad, Ganji Lakshmi Vara; Rajitha, Balney; Meenu, Madan; Rao, Manam Sreenivasa; Naik, Bannoth Reddya

    2009-08-17

    The tentative elucidation of the 3D-structure of vitellogenesis inhibiting hormone (VIH) peptides is conversely underprivileged by difficulties in gaining enough peptide or protein, diffracting crystals, and numerous extra technical aspects. As a result, no structural information is available for VIH peptide sequences registered in the Genbank. In this situation, it is not surprising that predictive methods have achieved great interest. Here, in this study the molt-inhibiting hormone (MIH) of the kuruma prawn (Marsupenaeus japonicus) is used, to predict the structure of four VIHrelated peptides in the crustacean species. The high similarity of the 3D-structures and the calculated physiochemical characteristics of these peptides suggest a common fold for the entire family.

  7. Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.

    Science.gov (United States)

    Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur

    2011-06-01

    Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

  8. Structural genomic variation in ischemic stroke

    Science.gov (United States)

    Matarin, Mar; Simon-Sanchez, Javier; Fung, Hon-Chung; Scholz, Sonja; Gibbs, J. Raphael; Hernandez, Dena G.; Crews, Cynthia; Britton, Angela; Wavrant De Vrieze, Fabienne; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Silliman, Scott; Case, L. Douglas; Hardy, John A.; Rich, Stephen S.; Meschia, James F.; Singleton, Andrew B.

    2008-01-01

    Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions;3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study. PMID:18288507

  9. Structures of peptide families by nuclear magnetic resonance spectroscopy and distance geometry

    Energy Technology Data Exchange (ETDEWEB)

    Pease, J.H.

    1989-12-01

    The three dimensional structures of several small peptides were determined using a combination of {sup 1}H nuclear magnetic resonance (NMR) and distance geometry calculations. These techniques were found to be particularly helpful for analyzing structural differences between related peptides since all of the peptides' {sup 1}H NMR spectra are very similar. The structures of peptides from two separate classes are presented. Peptides in the first class are related to apamin, an 18 amino acid peptide toxin from honey bee venom. The {sup 1}H NMR assignments and secondary structure determination of apamin were done previously. Quantitative NMR measurements and distance geometry calculations were done to calculate apamin's three dimensional structure. Peptides in the second class are 48 amino acid toxins from the sea anemone Radianthus paumotensis. The {sup 1}H NMR assignments of toxin II were done previously. The {sup 1}H NMR assignments of toxin III and the distance geometry calculations for both peptides are presented.

  10. Immune Response of Multiparous Hyper-Immunized Sows against Peptides from Non-Structural and Structural Proteins of PRRSV

    Directory of Open Access Journals (Sweden)

    Edgar Rascón-Castelo

    2015-11-01

    Full Text Available The purpose of this study was to evaluate the humoral and cellular responses of commercial multiparous and hyper-immunized sows against peptides from non-structural (nsp and structural proteins of porcine reproductive and respiratory syndrome virus (PRRSV. We selected sows with different numbers of parities from a commercial farm. Management practices on this farm include the use of the MLV commercial vaccine four times per year, plus two vaccinations during the acclimation period. The humoral response was evaluated via the antibody recognition of peptides from nsp and structural proteins, and the cellular response was assessed by measuring the frequency of peptide and PRRSV-specific IFN-gamma-secreting cells (IFNγ-SC. Our results show that sows with six parities have more antibodies against peptides from structural proteins than against peptides from nsp. The analysis of the cellular response revealed that the number of immunizations did not affect the frequency of IFNγ-SC and that the response was stronger against peptides from structural proteins (M protein than against nsp (nsp2. In summary, these results demonstrate that multiparous, hyper-immunized sows have a stronger immune humoral response to PRRSV structural peptides than nsp, but no differences in IFNγ-SC against the same peptides were observed.

  11. Pathways to Structure-Property Relationships of Peptide-Materials Interfaces: Challenges in Predicting Molecular Structures.

    Science.gov (United States)

    Walsh, Tiffany R

    2017-07-18

    An in-depth appreciation of how to manipulate the molecular-level recognition between peptides and aqueous materials interfaces, including nanoparticles, will advance technologies based on self-organized metamaterials for photonics and plasmonics, biosensing, catalysis, energy generation and harvesting, and nanomedicine. Exploitation of the materials-selective binding of biomolecules is pivotal to success in these areas and may be particularly key to producing new hierarchically structured biobased materials. These applications could be accomplished by realizing preferential adsorption of a given biomolecule onto one materials composition over another, one surface facet over another, or one crystalline polymorph over another. Deeper knowledge of the aqueous abiotic-biotic interface, to establish clear structure-property relationships in these systems, is needed to meet this goal. In particular, a thorough structural characterization of the surface-adsorbed peptides is essential for establishing these relationships but can often be challenging to accomplish via experimental approaches alone. In addition to myriad existing challenges associated with determining the detailed molecular structure of any molecule adsorbed at an aqueous interface, experimental characterization of materials-binding peptides brings new, complex challenges because many materials-binding peptides are thought to be intrinsically disordered. This means that these peptides are not amenable to experimental techniques that rely on the presence of well-defined secondary structure in the peptide when in the adsorbed state. To address this challenge, and in partnership with experiment, molecular simulations at the atomistic level can bring complementary and critical insights into the origins of this abiotic/biotic recognition and suggest routes for manipulating this phenomenon to realize new types of hybrid materials. For the reasons outlined above, molecular simulation approaches also face

  12. Structure of HLA-A*1101 in complex with a hepatitis B peptide homologue

    DEFF Research Database (Denmark)

    Blicher, Thomas; Kastrup, Jette Sandholm; Pedersen, Lars Østergaard

    2006-01-01

    A high-resolution structure of the human MHC-I molecule HLA-A*1101 is presented in which it forms a complex with a sequence homologue of a peptide that occurs naturally in hepatitis B virus DNA polymerase. The sequence of the bound peptide is AIMPARFYPK, while that of the corresponding natural...

  13. Diurnal Variations in Serum Glucose, Insulin and C-Peptide of Normal Korean Adults

    International Nuclear Information System (INIS)

    Choi, Du Hyok; Chung, June Key; Lee, Hong Kyu; Koh, Chang Soon; Hong, Kee Suk

    1983-01-01

    It is already well known that many factors are involved in maintaining normal blood glucose level. The amount and components of meal are also thought to be some of the factors which affect the blood glucose and insulin levels. It is reported that as for Koreans sugar takes up over 75% out of 2,098 kcal, the average daily calorie intake per adult. It implies that Koreans take a high-sugar diet compared with Westerners who take 40-50% of sugar out of their total average daily calorie. For the purpose of studying diurnal variations in serum glucose, insulin and C-peptide of normal Koreans adults based on ordinary Korean diet, we selected 13 normal Korean male adults and divided them into two groups, Group I (7 persons) and Group II (6 persons). We put Group I on 3,100 kcal and 75% sugar diet, and Group II on 2,100 kcal and 69% sugar diet per day for over 4 days. Serum glucose, insulin and C-peptide were checked every 30 minutes or every hour throughout 2 hour. Results are as follows: 1. As for serum glucose level, in the preprandial fasting state in the morning, mean±S.D. of Group I was 91.1±3.2 mg%, while that of Group II is 82.5±4.4 mg%. Both groups showed peaks of increased glucose level t postprandial 1 hour after each meal. The peak returned to the level shown during the fasting state at postprandial 1 hour after breakfast while the relatively high glucose levels were maintained respectively even for 2 or 3 hours after lunch and dinner. 2. As for serum insults level, Group I showed mean±S.D. of 14.7±3.0 μU/ml while Group II shows that of 7.0±2.6 μU/ml in the fasting state. Group I particularly showed the largest peak from preprandial a half or one and half an hour to postprandial one hour of lunch, and made relatively small peaks (47.7±10.8 μU/ml) at postprandial 1 hour after breakfast and dinner. No such large peak was marked in Group II, though it showed relatively similar patterns of peak after each meal. 3. As for C-peptide, in the fasting state

  14. Diurnal Variations in Serum Glucose, Insulin and C-Peptide of Normal Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Du Hyok; Chung, June Key; Lee, Hong Kyu; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Kee Suk [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1983-03-15

    It is already well known that many factors are involved in maintaining normal blood glucose level. The amount and components of meal are also thought to be some of the factors which affect the blood glucose and insulin levels. It is reported that as for Koreans sugar takes up over 75% out of 2,098 kcal, the average daily calorie intake per adult. It implies that Koreans take a high-sugar diet compared with Westerners who take 40-50% of sugar out of their total average daily calorie. For the purpose of studying diurnal variations in serum glucose, insulin and C-peptide of normal Koreans adults based on ordinary Korean diet, we selected 13 normal Korean male adults and divided them into two groups, Group I (7 persons) and Group II (6 persons). We put Group I on 3,100 kcal and 75% sugar diet, and Group II on 2,100 kcal and 69% sugar diet per day for over 4 days. Serum glucose, insulin and C-peptide were checked every 30 minutes or every hour throughout 2 hour. Results are as follows: 1. As for serum glucose level, in the preprandial fasting state in the morning, mean+-S.D. of Group I was 91.1+-3.2 mg%, while that of Group II is 82.5+-4.4 mg%. Both groups showed peaks of increased glucose level t postprandial 1 hour after each meal. The peak returned to the level shown during the fasting state at postprandial 1 hour after breakfast while the relatively high glucose levels were maintained respectively even for 2 or 3 hours after lunch and dinner. 2. As for serum insults level, Group I showed mean+-S.D. of 14.7+-3.0 muU/ml while Group II shows that of 7.0+-2.6 muU/ml in the fasting state. Group I particularly showed the largest peak from preprandial a half or one and half an hour to postprandial one hour of lunch, and made relatively small peaks (47.7+-10.8 muU/ml) at postprandial 1 hour after breakfast and dinner. No such large peak was marked in Group II, though it showed relatively similar patterns of peak after each meal. 3. As for C-peptide, in the fasting state

  15. Peptides actively transported across the tympanic membrane: Functional and structural properties.

    Directory of Open Access Journals (Sweden)

    Arwa Kurabi

    Full Text Available Otitis media (OM is the most common infectious disease of children under six, causing more antibiotic prescriptions and surgical procedures than any other pediatric condition. By screening a bacteriophage (phage library genetically engineered to express random peptides on their surfaces, we discovered unique peptides that actively transport phage particles across the intact tympanic membrane (TM and into the middle ear (ME. Herein our goals were to characterize the physiochemical peptide features that may underlie trans-TM phage transport; assess morphological and functional effects of phage peptides on the ME and inner ear (IE; and determine whether peptide-bearing phage transmigrate from the ME into the IE. Incubation of five peptide-bearing phage on the TM for over 4hrs resulted in demonstrably superior transport of one peptide, in level and in exponential increase over time. This suggests a preferred peptide motif for TM active transport. Functional and structural comparisons revealed unique features of this peptide: These include a central lysine residue, isoelectric point of 0.0 at physiological pH and a hydrophobic C-terminus. When the optimal peptide was applied to the TM independent of phage, similar transport was observed, indicating that integration into phage is not required. When 109 particles of the four different trans-TM phage were applied directly into the ME, no morphological effects were detected in the ME or IE when compared to saline or wild-type (WT phage controls. Comparable, reversible hearing loss was observed for saline controls, WT phage and trans-TM peptide phage, suggesting a mild conductive hearing loss due to ME fluid. Perilymph titers after ME incubation established that few copies of trans-TM peptide phage crossed into the IE. The results suggest that, within the parameters tested, trans-TM peptides are safe and could be used as potential agents for noninvasive delivery of drugs, particles and gene therapy

  16. Importance of Local Structural Variations on Recrystallization

    DEFF Research Database (Denmark)

    Juul Jensen, Dorte; Lin, Fengxiang; Zhang, Yubin

    2013-01-01

    Effects of local variations in the deformation microstructure on subsequent recrystallization are discussed and illustrated by three examples. The three examples consider local variations on different length scales and are: 1. Effects of local variations in the deformation microstructure on the f...

  17. Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

    Science.gov (United States)

    Xu, Peng; Andreasen, Peter A.; Huang, Mingdong

    2017-01-01

    This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively. The following affinity maturations significantly enhanced the potencies of the two peptides, 10-fold and >250-fold for upain-1 and mupain-1, respectively. The most potent muPA inhibitor has a potency (Ki = 2 nM) and specificity comparable to mono-clonal antibodies. Furthermore, we also found an unusual feature of mupain-1 that its inhibitory potency can be enhanced by increasing the flexibility, which challenges the traditional viewpoint that higher rigidity leading to higher affinity. Moreover, by changing a few key residues, we converted mupain-1 from a uPA inhibitor to inhibitors of other serine proteases, including plasma kallikrein (PK) and coagulation factor XIa (fXIa). PK and fXIa inhibitors showed Ki values in the low nanomolar range and high specificity. Our studies demonstrate the versatility of small cyclic peptides to engineer inhibitory potency against serine proteases and to provide a new strategy for generating peptide inhibitors of serine proteases. PMID:29104489

  18. Phase behavior and nanoscale structure of phospholipid membranes incorporated with acylated C-14-peptides

    DEFF Research Database (Denmark)

    Pedersen, T.B.; Kaasgaard, Thomas; Jensen, M.O.

    2005-01-01

    The thermotropic phase behavior and lateral structure of dipalmitoylphosphatidylcholine (DPPC) lipid bilayers containing an acylated peptide has been characterized by differential scanning calorimetry (DSC) on vesicles and atomic force microscopy (AFM) on mica-supported bilayers. The acylated...... peptide, which is a synthetic decapeptide N-terminally linked to a C-14 acyl chain (C-14-peptide), is incorporated into DPPC bilayers in amounts ranging from 0-20 mol %. The calorimetric scans of the two-component system demonstrate a distinct influence of the C-14-peptide on the lipid bilayer...... gel phase DPPC bilayers, inserts preferentially into preexisting defect regions and has a noticeable influence on the organization of the surrounding lipids. The presence of the C-14-peptide gives rise to a laterally heterogeneous bilayer structure with coexisting lipid domains characterized by a 10...

  19. Structural organization and spectroscopy of peptide-actinide(IV) complexes

    International Nuclear Information System (INIS)

    Dahou, S.

    2010-01-01

    The contamination of living organisms by actinide elements is at the origin of both radiological and chemical toxicity that may lead to severe dysfunction. Most of the data available on the actinide interaction with biological systems are macroscopic physiological measurements and are lacking a molecular description of the systems. Because of the intricacy of these systems, classical biochemical methods are difficult to implement. Our strategy consisted in designing simplified biomimetic peptides, and describing the corresponding intramolecular interactions with actinides. A carboxylic pentapeptide of the form DDPDD has been at the starting point of this work in order to further assess the influence of the peptide sequence on the topology of the complexes.To do so, various linear (Asp/Ala permutations, peptoids) and cyclic analogues have been synthesized. Furthermore, in order to include the hydroxamic function (with a high affinity for Fe(III)) in the peptide, both desferrioxamine and acetohydroxamic acid have been investigated. However because of difficulties in synthesis, we have not been able to test these peptides. Three actinide cations have been considered at oxidation state +IV (Th, Np, Pu) and compared to Fe(III), often considered as a biological surrogate of Pu(IV). The spatial arrangement of the peptide around the cation has been probed by spectrophotometry and X-ray Absorption Spectroscopy. The spectroscopic data and EXAFS data adjustment lead us to rationalize the topology of the complexes as a function of the peptide sequence: mix hydroxy polynuclear species for linear and cyclic peptides, mononuclear for the desferrioxamine complexes. Furthermore, significant differences have appeared between Fe(III) and actinide(IV), related to differences of reactivity in aqueous medium. (author)

  20. Structural and Pharmacological Effects of Ring-Closing Metathesis in Peptides

    Directory of Open Access Journals (Sweden)

    Pål Rongved

    2010-09-01

    Full Text Available Applications of ring-closing alkene metathesis (RCM in acyclic α- and β-peptides and closely related systems are reviewed, with a special emphasis on the structural and pharmacological effects of cyclization by RCM.

  1. Identification and accurate quantification of structurally related peptide impurities in synthetic human C-peptide by liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Li, Ming; Josephs, Ralf D; Daireaux, Adeline; Choteau, Tiphaine; Westwood, Steven; Wielgosz, Robert I; Li, Hongmei

    2018-06-04

    Peptides are an increasingly important group of biomarkers and pharmaceuticals. The accurate purity characterization of peptide calibrators is critical for the development of reference measurement systems for laboratory medicine and quality control of pharmaceuticals. The peptides used for these purposes are increasingly produced through peptide synthesis. Various approaches (for example mass balance, amino acid analysis, qNMR, and nitrogen determination) can be applied to accurately value assign the purity of peptide calibrators. However, all purity assessment approaches require a correction for structurally related peptide impurities in order to avoid biases. Liquid chromatography coupled to high resolution mass spectrometry (LC-hrMS) has become the key technique for the identification and accurate quantification of structurally related peptide impurities in intact peptide calibrator materials. In this study, LC-hrMS-based methods were developed and validated in-house for the identification and quantification of structurally related peptide impurities in a synthetic human C-peptide (hCP) material, which served as a study material for an international comparison looking at the competencies of laboratories to perform peptide purity mass fraction assignments. More than 65 impurities were identified, confirmed, and accurately quantified by using LC-hrMS. The total mass fraction of all structurally related peptide impurities in the hCP study material was estimated to be 83.3 mg/g with an associated expanded uncertainty of 3.0 mg/g (k = 2). The calibration hierarchy concept used for the quantification of individual impurities is described in detail. Graphical abstract ᅟ.

  2. Quantitative Structure-Activity Relationships and Docking Studies of Calcitonin Gene-Related Peptide Antagonists

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

    Defining the role of calcitonin gene-related peptide in migraine pathogenesis could lead to the application of calcitonin gene-related peptide antagonists as novel migraine therapeutics. In this work, quantitative structure-activity relationship modeling of biological activities of a large range...... of calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression....... The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model...

  3. Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin.

    Science.gov (United States)

    Haney, Evan F; Nazmi, Kamran; Bolscher, Jan G M; Vogel, Hans J

    2012-03-01

    Lactoferricin and lactoferrampin are two antimicrobial peptides found in the N-terminal lobe of bovine lactoferrin with broad spectrum antimicrobial activity against a range of Gram-positive and Gram-negative bacteria as well as Candida albicans. A heterodimer comprised of lactoferrampin joined to a fragment of lactoferricin was recently reported in which these two peptides were joined at their C-termini through the two amino groups of a single Lys residue (Bolscher et al., 2009, Biochimie 91(1):123-132). This hybrid peptide, termed LFchimera, has significantly higher antimicrobial activity compared to the individual peptides or an equimolar mixture of the two. In this work, the underlying mechanism behind the increased antibacterial activity of LFchimera was investigated. Differential scanning calorimetry studies demonstrated that all the peptides influenced the thermotropic phase behaviour of anionic phospholipid suspensions. Calcein leakage and vesicle fusion experiments with anionic liposomes revealed that LFchimera had enhanced membrane perturbing properties compared to the individual peptides. Peptide structures were evaluated using circular dichroism and NMR spectroscopy to gain insight into the structural features of LFchimera that contribute to the increased antimicrobial activity. The NMR solution structure, determined in a miscible co-solvent mixture of chloroform, methanol and water, revealed that the Lys linkage increased the helical content in LFchimera compared to the individual peptides, but it did not fix the relative orientations of lactoferricin and lactoferrampin with respect to each other. The structure of LFchimera provides insight into the conformation of this peptide in a membranous environment and improves our understanding of its antimicrobial mechanism of action. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Combining UV photodissociation with electron transfer for peptide structure analysis

    Czech Academy of Sciences Publication Activity Database

    Shaffer, C. J.; Marek, Aleš; Pepin, R.; Slováková, K.; Tureček, F.

    2015-01-01

    Roč. 50, č. 3 (2015), s. 470-475 ISSN 1076-5174 Institutional support: RVO:61388963 Keywords : electron transfer dissociation * laser photodissociation * peptide ions * cation radical * chromophores * isomer distinction Subject RIV: CE - Biochemistry Impact factor: 2.541, year: 2015

  5. Rapid discovery of peptide capture candidates with demonstrated specificity for structurally similar toxins

    Science.gov (United States)

    Sarkes, Deborah A.; Hurley, Margaret M.; Coppock, Matthew B.; Farrell, Mikella E.; Pellegrino, Paul M.; Stratis-Cullum, Dimitra N.

    2016-05-01

    Peptides have emerged as viable alternatives to antibodies for molecular-based sensing due to their similarity in recognition ability despite their relative structural simplicity. Various methods for peptide capture reagent discovery exist, including phage display, yeast display, and bacterial display. One of the primary advantages of peptide discovery by bacterial display technology is the speed to candidate peptide capture agent, due to both rapid growth of bacteria and direct utilization of the sorted cells displaying each individual peptide for the subsequent round of biopanning. We have previously isolated peptide affinity reagents towards protective antigen of Bacillus anthracis using a commercially available automated magnetic sorting platform with improved enrichment as compared to manual magnetic sorting. In this work, we focus on adapting our automated biopanning method to a more challenging sort, to demonstrate the specificity possible with peptide capture agents. This was achieved using non-toxic, recombinant variants of ricin and abrin, RiVax and abrax, respectively, which are structurally similar Type II ribosomal inactivating proteins with significant sequence homology. After only two rounds of biopanning, enrichment of peptide capture candidates binding abrax but not RiVax was achieved as demonstrated by Fluorescence Activated Cell Sorting (FACS) studies. Further sorting optimization included negative sorting against RiVax, proper selection of autoMACS programs for specific sorting rounds, and using freshly made buffer and freshly thawed protein target for each round of biopanning for continued enrichment over all four rounds. Most of the resulting candidates from biopanning for abrax binding peptides were able to bind abrax but not RiVax, demonstrating that short peptide sequences can be highly specific even at this early discovery stage.

  6. Structure of genes for dermaseptins B, antimicrobial peptides from frog skin. Exon 1-encoded prepropeptide is conserved in genes for peptides of highly different structures and activities.

    Science.gov (United States)

    Vouille, V; Amiche, M; Nicolas, P

    1997-09-01

    We cloned the genes of two members of the dermaseptin family, broad-spectrum antimicrobial peptides isolated from the skin of the arboreal frog Phyllomedusa bicolor. The dermaseptin gene Drg2 has a 2-exon coding structure interrupted by a small 137-bp intron, wherein exon 1 encoded a 22-residue hydrophobic signal peptide and the first three amino acids of the acidic propiece; exon 2 contained the 18 additional acidic residues of the propiece plus a typical prohormone processing signal Lys-Arg and a 32-residue dermaseptin progenitor sequence. The dermaseptin genes Drg2 and Drg1g2 have conserved sequences at both untranslated ends and in the first and second coding exons. In contrast, Drg1g2 comprises a third coding exon for a short version of the acidic propiece and a second dermaseptin progenitor sequence. Structural conservation between the two genes suggests that Drg1g2 arose recently from an ancestral Drg2-like gene through amplification of part of the second coding exon and 3'-untranslated region. Analysis of the cDNAs coding precursors for several frog skin peptides of highly different structures and activities demonstrates that the signal peptides and part of the acidic propieces are encoded by conserved nucleotides encompassed by the first coding exon of the dermaseptin genes. The organization of the genes that belong to this family, with the signal peptide and the progenitor sequence on separate exons, permits strikingly different peptides to be directed into the secretory pathway. The recruitment of such a homologous 'secretory' exon by otherwise non-homologous genes may have been an early event in the evolution of amphibian.

  7. Designed beta-boomerang antiendotoxic and antimicrobial peptides: structures and activities in lipopolysaccharide.

    Science.gov (United States)

    Bhunia, Anirban; Mohanram, Harini; Domadia, Prerna N; Torres, Jaume; Bhattacharjya, Surajit

    2009-08-14

    Lipopolysaccharide (LPS), an integral part of the outer membrane of Gram-negative bacteria, is involved in a variety of biological processes including inflammation, septic shock, and resistance to host-defense molecules. LPS also provides an environment for folding of outer membrane proteins. In this work, we describe the structure-activity correlation of a series of 12-residue peptides in LPS. NMR structures of the peptides derived in complex with LPS reveal boomerang-like beta-strand conformations that are stabilized by intimate packing between the two aromatic residues located at the 4 and 9 positions. This structural feature renders these peptides with a high ability to neutralize endotoxicity, >80% at 10 nM concentration, of LPS. Replacements of these aromatic residues either with Ala or with Leu destabilizes the boomerang structure with the concomitant loss of antiendotoxic and antimicrobial activities. Furthermore, the aromatic packing stabilizing the beta-boomerang structure in LPS is found to be maintained even in a truncated octapeptide, defining a structured LPS binding motif. The mode of action of the active designed peptides correlates well with their ability to perturb LPS micelle structures. Fourier transform infrared spectroscopy studies of the peptides delineate beta-type conformations and immobilization of phosphate head groups of LPS. Trp fluorescence studies demonstrated selective interactions with LPS and the depth of insertion into the LPS bilayer. Our results demonstrate the requirement of LPS-specific structures of peptides for endotoxin neutralizations. In addition, we propose that structures of these peptides may be employed to design proteins for the outer membrane.

  8. Nuclear Magnetic Resonance structural studies of peptides and proteins from the vaso-regulatory System

    International Nuclear Information System (INIS)

    Sizun, Philippe

    1991-01-01

    The aim of the present work is to show how Nuclear Magnetic Resonance (NMR) allows to determine the 3D structure of peptides and proteins in solution. A comparative study of peptides involved in the vaso-regulatory System (form small hormonal peptide to the 65 amido-acid protein hirudin) has allowed to design most efficient NMR 1D and 2D strategies. It rapidly appeared that the size of the peptide plays a key role in the structuration of the molecule, smallest peptides being weakly structured owing to the lack of cooperative effects. As the molecular size increases or if conformational locks are present (disulfide bridges) the probability of stable secondary structure increases. For the protein hirudin, a combination of ail available NMR parameters deduced form dedicated experiments (chemical shifts, coupling constants, overhauser effects, accessibility of amide protons) and molecular modelling under constraints allows a clear 3D structure to be proposed for this protein in solution. Finally, a comparative study of the experimental structures and of those deduced form prediction rules has shed light on the concept of structural predisposition, the latter being of high value for a better understanding of structure-activity relationships. (author) [fr

  9. Buckwheat trypsin inhibitor with helical hairpin structure belongs to a new family of plant defence peptides.

    Science.gov (United States)

    Oparin, Peter B; Mineev, Konstantin S; Dunaevsky, Yakov E; Arseniev, Alexander S; Belozersky, Mikhail A; Grishin, Eugene V; Egorov, Tsezi A; Vassilevski, Alexander A

    2012-08-15

    A new peptide trypsin inhibitor named BWI-2c was obtained from buckwheat (Fagopyrum esculentum) seeds by sequential affinity, ion exchange and reversed-phase chromatography. The peptide was sequenced and found to contain 41 amino acid residues, with four cysteine residues involved in two intramolecular disulfide bonds. Recombinant BWI-2c identical to the natural peptide was produced in Escherichia coli in a form of a cleavable fusion with thioredoxin. The 3D (three-dimensional) structure of the peptide in solution was determined by NMR spectroscopy, revealing two antiparallel α-helices stapled by disulfide bonds. Together with VhTI, a trypsin inhibitor from veronica (Veronica hederifolia), BWI-2c represents a new family of protease inhibitors with an unusual α-helical hairpin fold. The linker sequence between the helices represents the so-called trypsin inhibitory loop responsible for direct binding to the active site of the enzyme that cleaves BWI-2c at the functionally important residue Arg(19). The inhibition constant was determined for BWI-2c against trypsin (1.7×10(-1)0 M), and the peptide was tested on other enzymes, including those from various insect digestive systems, revealing high selectivity to trypsin-like proteases. Structural similarity shared by BWI-2c, VhTI and several other plant defence peptides leads to the acknowledgement of a new widespread family of plant peptides termed α-hairpinins.

  10. Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Tatiana Radchenko

    Full Text Available Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability. For this purpose, several in-silico software tools have been developed such as PeptideCutter or PoPS, which aim to predict peptide cleavage sites for different proteases. Moreover, several databases exist where this information is collected and stored from public sources such as MEROPS and ExPASy ENZYME databases. These tools can help design a peptide drug with increased stability against proteolysis, though they are limited to natural amino acids or cannot process cyclic peptides, for example. We worked to develop a new methodology to analyze peptide structure and amide bond metabolic stability based on the peptide structure (linear/cyclic, natural/unnatural amino acids. This approach used liquid chromatography / high resolution, mass spectrometry to obtain the analytical data from in vitro incubations. We collected experimental data for a set (linear/cyclic, natural/unnatural amino acids of fourteen peptide drugs and four substrate peptides incubated with different proteolytic media: trypsin, chymotrypsin, pepsin, pancreatic elastase, dipeptidyl peptidase-4 and neprilysin. Mass spectrometry data was analyzed to find metabolites and determine their structures, then all the results were stored in a chemically aware manner, which allows us to compute the peptide bond susceptibility by using a frequency analysis of the metabolic-liable bonds. In total 132 metabolites were found from the various in vitro conditions tested resulting in 77 distinct cleavage sites. The most frequent observed cleavage sites agreed with those reported in the literature. The

  11. Structure of the antimicrobial beta-hairpin peptide protegrin-1 in a DLPC lipid bilayer investigated by molecular dynamics simulation

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N

    2007-01-01

    -550]), and to delineate specific peptide-membrane interactions which are responsible for the peptide's membrane binding properties. A novel, previously unknown, "kick" shaped conformation of the peptide was detected, where a bend at the C-terminal beta-strand of the peptide caused the peptide backbone at residues 16...... different initial orientations of the peptide converged to the same final equilibrium orientation of the peptide relative to the bilayer. The kick-shaped conformation was observed only in one of the two simulations....... of the peptide in a membrane environment (previously solved only in solution [R.L. Fahrner, T. Dieckmann, S.S.L. Harwig, R.I. Lehrer, D. Eisenberg, J. Feigon, Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes. Chemistry and Biology, 3 (1996) 543...

  12. Child Development and Structural Variation in the Human Genome

    Science.gov (United States)

    Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

    2013-01-01

    Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

  13. Structure-function characterization and optimization of a plant-derived antibacterial peptide.

    Science.gov (United States)

    Suarez, Mougli; Haenni, Marisa; Canarelli, Stéphane; Fisch, Florian; Chodanowski, Pierre; Servis, Catherine; Michielin, Olivier; Freitag, Ruth; Moreillon, Philippe; Mermod, Nicolas

    2005-09-01

    Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.

  14. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering.

    Science.gov (United States)

    Gao, Xiang; Zhang, Xiaohong; Song, Jinlin; Xu, Xiao; Xu, Anxiu; Wang, Mengke; Xie, Bingwu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2015-01-01

    The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.

  15. Variations in the Circumplex Structure of Mood.

    Science.gov (United States)

    Feldman, Lisa A.

    1995-01-01

    Researchers have emphasized the similarity of the semantic and self-report mood circumplexes. Study investigated systematic differences in theses structures. Demonstrated that when making judgments of their mood, people weigh the arousal dimension less than the valence dimension. Dimensions are weighed equally in semantic structure. (JBJ)

  16. Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese.

    Science.gov (United States)

    Saito, T; Nakamura, T; Kitazawa, H; Kawai, Y; Itoh, T

    2000-07-01

    Seven kinds of ripened cheeses (8-mo-aged and 24-mo-aged Gouda, Emmental, Blue, Camembert, Edam, and Havarti) were homogenized with distilled water, and water-soluble peptides were prepared by C-18 hydrophobic chromatography. The inhibitory activity to angiotensin I-converting enzyme and decrease in the systolic blood pressure in spontaneously hypertensive rats were measured before and after oral administration of each peptide sample. The strongest depressive effect in the systolic blood pressure (-24.7 mm Hg) and intensive inhibitory activity to angiotensin I-converting enzyme (75.7%) were detected in the peptides from 8-mo-aged Gouda cheese. Four peptides were isolated by HPLC with reverse-phase and gel filtration modes. Their chemical structures and origins, clarified by combination analyses of protein sequencing, amino acid composition, and mass spectrometry, were as follows: peptide A, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln [alpha(s1)-casein (CN), B-8P; f 1-9]; peptide B, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln-Gly-Leu-Pro-Gln (alpha(s1)-CN, B-8P; f 1-13); peptide F, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn (beta-CN, A2-5P; f 60-68); and peptide G, Met-Pro-Phe-Pro-Lys-Tyr-Pro-Val-Gln-Pro-Phe (beta-CN, A2-5P; f 109-119). Peptides A and F, which were chemically synthesized, showed potent angiotensin I-converting enzyme inhibitory activity with little antihypertensive effects.

  17. Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiansheng; Natarajan, Kannan; Boyd, Lisa F.; Morozov, Giora I.; Mage, Michael G.; Margulies, David H. (NIH); (Hebrew)

    2017-10-12

    Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.

  18. The structural basis for peptide selection by the transport receptor OppA

    NARCIS (Netherlands)

    Berntsson, Ronnie P-A; Doeven, Mark K.; Fusetti, Fabrizia; Duurkens, Ria H.; Sengupta, Durba; Marrink, Siewert-Jan; Thunnissen, Andy-Mark W. H.; Poolman, Bert; Slotboom, Dirk-Jan

    2009-01-01

    Oligopeptide-binding protein A (OppA) from Lactococcus lactis binds peptides of an exceptionally wide range of lengths (4-35 residues), with no apparent sequence preference. Here, we present the crystal structures of OppA in the open-and closed-liganded conformations. The structures directly explain

  19. Structural Basis for Antigenic Peptide Recognition and Processing by Endoplasmic Reticulum (ER) Aminopeptidase 2.

    Science.gov (United States)

    Mpakali, Anastasia; Giastas, Petros; Mathioudakis, Nikolas; Mavridis, Irene M; Saridakis, Emmanuel; Stratikos, Efstratios

    2015-10-23

    Endoplasmic reticulum (ER) aminopeptidases process antigenic peptide precursors to generate epitopes for presentation by MHC class I molecules and help shape the antigenic peptide repertoire and cytotoxic T-cell responses. To perform this function, ER aminopeptidases have to recognize and process a vast variety of peptide sequences. To understand how these enzymes recognize substrates, we determined crystal structures of ER aminopeptidase 2 (ERAP2) in complex with a substrate analogue and a peptidic product to 2.5 and 2.7 Å, respectively, and compared them to the apo-form structure determined to 3.0 Å. The peptides were found within the internal cavity of the enzyme with no direct access to the outside solvent. The substrate analogue extends away from the catalytic center toward the distal end of the internal cavity, making interactions with several shallow pockets along the path. A similar configuration was evident for the peptidic product, although decreasing electron density toward its C terminus indicated progressive disorder. Enzymatic analysis confirmed that visualized interactions can either positively or negatively impact in vitro trimming rates. Opportunistic side-chain interactions and lack of deep specificity pockets support a limited-selectivity model for antigenic peptide processing by ERAP2. In contrast to proposed models for the homologous ERAP1, no specific recognition of the peptide C terminus by ERAP2 was evident, consistent with functional differences in length selection and self-activation between these two enzymes. Our results suggest that ERAP2 selects substrates by sequestering them in its internal cavity and allowing opportunistic interactions to determine trimming rates, thus combining substrate permissiveness with sequence bias. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Structural Characterization and Disulfide Assignment of Spider Peptide Phα1β by Mass Spectrometry

    Science.gov (United States)

    Wormwood, Kelly L.; Ngounou Wetie, Armand Gatien; Gomez, Marcus Vinicius; Ju, Yue; Kowalski, Paul; Mihasan, Marius; Darie, Costel C.

    2018-05-01

    Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1β peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1β peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1β peptide. These experiments provide essential structural information about Phα1β and may assist in providing insight into the peptide's analgesic effect with very low side effects. [Figure not available: see fulltext.

  1. Predicting binding within disordered protein regions to structurally characterised peptide-binding domains.

    Directory of Open Access Journals (Sweden)

    Waqasuddin Khan

    Full Text Available Disordered regions of proteins often bind to structured domains, mediating interactions within and between proteins. However, it is difficult to identify a priori the short disordered regions involved in binding. We set out to determine if docking such peptide regions to peptide binding domains would assist in these predictions.We assembled a redundancy reduced dataset of SLiM (Short Linear Motif containing proteins from the ELM database. We selected 84 sequences which had an associated PDB structures showing the SLiM bound to a protein receptor, where the SLiM was found within a 50 residue region of the protein sequence which was predicted to be disordered. First, we investigated the Vina docking scores of overlapping tripeptides from the 50 residue SLiM containing disordered regions of the protein sequence to the corresponding PDB domain. We found only weak discrimination of docking scores between peptides involved in binding and adjacent non-binding peptides in this context (AUC 0.58.Next, we trained a bidirectional recurrent neural network (BRNN using as input the protein sequence, predicted secondary structure, Vina docking score and predicted disorder score. The results were very promising (AUC 0.72 showing that multiple sources of information can be combined to produce results which are clearly superior to any single source.We conclude that the Vina docking score alone has only modest power to define the location of a peptide within a larger protein region known to contain it. However, combining this information with other knowledge (using machine learning methods clearly improves the identification of peptide binding regions within a protein sequence. This approach combining docking with machine learning is primarily a predictor of binding to peptide-binding sites, and is not intended as a predictor of specificity of binding to particular receptors.

  2. Collagencin, an antibacterial peptide from fish collagen: Activity, structure and interaction dynamics with membrane

    International Nuclear Information System (INIS)

    Ennaas, Nadia; Hammami, Riadh; Gomaa, Ahmed; Bédard, François; Biron, Éric; Subirade, Muriel; Beaulieu, Lucie; Fliss, Ismail

    2016-01-01

    In this study, we first report characterization of collagencin, an antimicrobial peptide identified from fish collagen hydrolysate. The peptide completely inhibited the growth of Staphylococcus aureus at 1.88 mM. Although non-toxic up to 470 μM, collagencin was hemolytic at higher concentrations. The secondary structure of collagencin was mainly composed by β-sheet and β-turn as determined by CD measurements and molecular dynamics. The peptide is likely to form β-sheet structure under hydrophobic environments and interacts with both anionic (phosphatidylglycerol) and zwitterionic (phosphoethanolamine and phosphatidylcholine) lipids as shown with CD spectroscopy and molecular dynamics. The peptide formed several hydrogen bonds with both POPG and POPE lipids and remained at membrane–water interface, suggesting that collagencin antibacterial action follows a carpet mechanism. Collagenous fish wastes could be processed by enzymatic hydrolysis and transformed into products of high value having functional or biological properties. Marine collagens are a promising source of antimicrobial peptides with new implications in food safety and human health. - Highlights: • Collagencin, an antibacterial (G+ & G-) peptide identified from fish collagen hydrolysate. • The peptide completely inhibited the growth of S. aureus at 1.88 mM and non-toxic at 470 μM. • The secondary structure was mainly composed by β-sheet and turn as determined by CD and MD. • Collagencin interacts with both anionic and zwitterionic lipids as shown with CD and MD. • Collagencin antibacterial action probably follows a carpet mechanism.

  3. Collagencin, an antibacterial peptide from fish collagen: Activity, structure and interaction dynamics with membrane

    Energy Technology Data Exchange (ETDEWEB)

    Ennaas, Nadia [STELA Dairy Research Centre, Institute of Nutrition and Functional Foods, Université Laval, G1V 0A6 Québec, QC (Canada); Hammami, Riadh, E-mail: riadh.hammami@fsaa.ulaval.ca [STELA Dairy Research Centre, Institute of Nutrition and Functional Foods, Université Laval, G1V 0A6 Québec, QC (Canada); Gomaa, Ahmed [STELA Dairy Research Centre, Institute of Nutrition and Functional Foods, Université Laval, G1V 0A6 Québec, QC (Canada); Bédard, François; Biron, Éric [Faculty of Pharmacy, Université Laval and Laboratory of Medicinal Chemistry, CHU de Québec Research Centre, G1V 4G2 Québec, QC (Canada); Subirade, Muriel [STELA Dairy Research Centre, Institute of Nutrition and Functional Foods, Université Laval, G1V 0A6 Québec, QC (Canada); Beaulieu, Lucie, E-mail: lucie.beaulieu@fsaa.ulaval.ca [STELA Dairy Research Centre, Institute of Nutrition and Functional Foods, Université Laval, G1V 0A6 Québec, QC (Canada); Department of Biology, Chemistry and Geography, Université du Québec à Rimouski (UQAR), 300 Allée des Ursulines, Rimouski, QC G5L 3A1 (Canada); Fliss, Ismail, E-mail: ismail.fliss@fsaa.ulaval.ca [STELA Dairy Research Centre, Institute of Nutrition and Functional Foods, Université Laval, G1V 0A6 Québec, QC (Canada)

    2016-04-29

    In this study, we first report characterization of collagencin, an antimicrobial peptide identified from fish collagen hydrolysate. The peptide completely inhibited the growth of Staphylococcus aureus at 1.88 mM. Although non-toxic up to 470 μM, collagencin was hemolytic at higher concentrations. The secondary structure of collagencin was mainly composed by β-sheet and β-turn as determined by CD measurements and molecular dynamics. The peptide is likely to form β-sheet structure under hydrophobic environments and interacts with both anionic (phosphatidylglycerol) and zwitterionic (phosphoethanolamine and phosphatidylcholine) lipids as shown with CD spectroscopy and molecular dynamics. The peptide formed several hydrogen bonds with both POPG and POPE lipids and remained at membrane–water interface, suggesting that collagencin antibacterial action follows a carpet mechanism. Collagenous fish wastes could be processed by enzymatic hydrolysis and transformed into products of high value having functional or biological properties. Marine collagens are a promising source of antimicrobial peptides with new implications in food safety and human health. - Highlights: • Collagencin, an antibacterial (G+ & G-) peptide identified from fish collagen hydrolysate. • The peptide completely inhibited the growth of S. aureus at 1.88 mM and non-toxic at 470 μM. • The secondary structure was mainly composed by β-sheet and turn as determined by CD and MD. • Collagencin interacts with both anionic and zwitterionic lipids as shown with CD and MD. • Collagencin antibacterial action probably follows a carpet mechanism.

  4. Structural Characterization and Disulfide Assignment of Spider Peptide Phα1β by Mass Spectrometry

    Science.gov (United States)

    Wormwood, Kelly L.; Ngounou Wetie, Armand Gatien; Gomez, Marcus Vinicius; Ju, Yue; Kowalski, Paul; Mihasan, Marius; Darie, Costel C.

    2018-04-01

    Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1β peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1β peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1β peptide. These experiments provide essential structural information about Phα1β and may assist in providing insight into the peptide's analgesic effect with very low side effects. [Figure not available: see fulltext.

  5. Structural analysis and taste evaluation of γ-glutamyl peptides comprising sulfur-containing amino acids.

    Science.gov (United States)

    Amino, Yusuke; Wakabayashi, Hidehiko; Akashi, Satoko; Ishiwatari, Yutaka

    2018-03-01

    The structures, flavor-modifying effects, and CaSR activities of γ-glutamyl peptides comprising sulfur-containing amino acids were investigated. The chemical structures, including the linkage mode of the N-terminal glutamic acid, of γ-L-glutamyl-S-(2-propenyl)-L-cysteine (γ-L-glutamyl-S-allyl-L-cysteine) and its sulfoxide isolated from garlic were established by comparing their NMR spectra with those of authentic peptides prepared using chemical methods. Mass spectrometric analysis also enabled determination of the linkage modes in the glutamyl dipeptides by their characteristic fragmentation. In sensory evaluation, these peptides exhibited flavor-modifying effects (continuity) in umami solutions less pronounced but similar to that of glutathione. Furthermore, the peptides exhibited intrinsic flavor due to the sulfur-containing structure, which may be partially responsible for their flavor-modifying effects. In CaSR assays, γ-L-glutamyl-S-methyl-L-cysteinylglycine was most active, which indicates that the presence of a medium-sized aliphatic substituent at the second amino acid residue in γ-glutamyl peptides enhances CaSR activity.

  6. Structure and dynamics of cationic membrane peptides and proteins: Insights from solid-state NMR

    Science.gov (United States)

    Hong, Mei; Su, Yongchao

    2011-01-01

    Many membrane peptides and protein domains contain functionally important cationic Arg and Lys residues, whose insertion into the hydrophobic interior of the lipid bilayer encounters significant energy barriers. To understand how these cationic molecules overcome the free energy barrier to insert into the lipid membrane, we have used solid-state NMR spectroscopy to determine the membrane-bound topology of these peptides. A versatile array of solid-state NMR experiments now readily yields the conformation, dynamics, orientation, depth of insertion, and site-specific protein–lipid interactions of these molecules. We summarize key findings of several Arg-rich membrane peptides, including β-sheet antimicrobial peptides, unstructured cell-penetrating peptides, and the voltage-sensing helix of voltage-gated potassium channels. Our results indicate the central role of guanidinium-phosphate and guanidinium-water interactions in dictating the structural topology of these cationic molecules in the lipid membrane, which in turn account for the mechanisms of this functionally diverse class of membrane peptides. PMID:21344534

  7. A Novel MS-Cleavable Azo Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS)

    Science.gov (United States)

    Iacobucci, Claudio; Hage, Christoph; Schäfer, Mathias; Sinz, Andrea

    2017-10-01

    The chemical cross-linking/mass spectrometry (MS) approach is a growing research field in structural proteomics that allows gaining insights into protein conformations. It relies on creating distance constraints between cross-linked amino acid side chains that can further be used to derive protein structures. Currently, the most urgent task for designing novel cross-linking principles is an unambiguous and automated assignment of the created cross-linked products. Here, we introduce the homobifunctional, amine-reactive, and water soluble cross-linker azobisimidoester (ABI) as a prototype of a novel class of cross-linkers. The ABI-linker possesses an innovative modular scaffold combining the benefits of collisional activation lability with open shell chemistry. This MS-cleavable cross-linker can be efficiently operated via free radical initiated peptide sequencing (FRIPS) in positive ionization mode. Our proof-of-principle study challenges the gas phase behavior of the ABI-linker for the three amino acids, lysine, leucine, and isoleucine, as well as the model peptide thymopentin. The isomeric amino acids leucine and isoleucine could be discriminated by their characteristic side chain fragments. Collisional activation experiments were conducted via positive electrospray ionization (ESI) on two Orbitrap mass spectrometers. The ABI-mediated formation of odd electron product ions in MS/MS and MS3 experiments was evaluated and compared with a previously described azo-based cross-linker. All cross-linked products were amenable to automated analysis by the MeroX software, underlining the future potential of the ABI-linker for structural proteomics studies. [Figure not available: see fulltext.

  8. Amyloid–β peptides time-dependent structural modifications: AFM and voltammetric characterization

    Energy Technology Data Exchange (ETDEWEB)

    Enache, Teodor Adrian; Chiorcea-Paquim, Ana-Maria; Oliveira-Brett, Ana Maria, E-mail: brett@ci.uc.pt

    2016-07-05

    The human amyloid beta (Aβ) peptides, Aβ{sub 1-40} and Aβ{sub 1-42}, structural modifications, from soluble monomers to fully formed fibrils through intermediate structures, were investigated, and the results were compared with those obtained for the inverse Aβ{sub 40-1} and Aβ{sub 42-1}, mutant Aβ{sub 1-40}Phe{sup 10} and Aβ{sub 1-40}Nle{sup 35}, and rat Aβ{sub 1-40}Rat peptide sequences. The aggregation was followed at a slow rate, in chloride free media and room temperature, and revealed to be a sequence-structure process, dependent on the physicochemical properties of each Aβ peptide isoforms, and occurring at different rates and by different pathways. The fibrilization process was investigated by atomic force microscopy (AFM), via changes in the adsorption morphology from: (i) initially random coiled structures of ∼0.6 nm height, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to (ii) aggregates and protofibrils of 1.5–6.0 nm height and (iii) two types of fibrils, corresponding to the Aβ peptide in a β-sheet configuration. The reactivity of the carbon electrode surface was considered. The hydrophobic surface induced rapid changes of the Aβ peptide conformations, and differences between the adsorbed fibrils, formed at the carbon surface (beaded, thin, <2.0 nm height) or in solution (long, smooth, thick, >2.0 nm height), were detected. Differential pulse voltammetry showed that, according to their primary structure, the Aβ peptides undergo oxidation in one or two steps, the first step corresponding to the tyrosine amino acids oxidation, and the second one to the histidine and methionine amino acids oxidation. The fibrilization process was electrochemically detected via the decrease of the Aβ peptide oxidation peak currents that occurred in a time dependent manner. - Highlights: • The Aβ peptide fibrilization process was followed by AFM and DP voltammetry. • The human Aβ{sub 1-40} and Aβ{sub 1

  9. Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.

    Science.gov (United States)

    Wu, J W; Cocina, A E; Chai, J; Hay, B A; Shi, Y

    2001-07-01

    The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with the second BIR domain (BIR2) playing an important role. Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself and in complex with the N-terminal peptides from Hid and Grim reveal that these peptides bind a surface groove on DIAP1, with the first four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interactions. Interestingly, peptide binding induces the formation of an additional alpha helix in DIAP1. Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins.

  10. Structural variations in nanosized confined gallium

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Min Kai [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China); Tien Cheng [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China)] [Center for Micro/Nano Science of Technology, National Cheng Kung University, Tainan 70101, Taiwan, ROC (China); Charnaya, E.V., E-mail: charnaya@live.co [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China)] [Institute of Physics, St. Petersburg State University, St. Petersburg, Petrodvorets 198504 (Russian Federation); Sheu, Hwo-Shuenn [National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan (China); Kumzerov, Yu.A. [A.F. Ioffe Physico-Technical Institute RAS, St. Petersburg, 194021 (Russian Federation)

    2010-03-29

    The complex crystalline structure of gallium under nanoconfinement was revealed by synchrotron radiation x-ray powder diffraction. Nanoconfinement was shown to stabilize delta-Ga which is metastable in bulk. Two new gallium phases named iota- and kappa-Ga were found upon cooling below room temperature. These crystalline modifications were stable and coexisted with known gallium phases. Correlations between confined gallium particle shapes and emergence of particular crystalline phases were observed. Melting and freezing temperatures for different gallium phases were obtained. Remarkable supercooling of liquid gallium was seen in 3.5 nm pores.

  11. Structural characterization by NMR of a double phosphorylated chimeric peptide vaccine for treatment of Alzheimer's disease.

    Science.gov (United States)

    Ramírez-Gualito, Karla; Richter, Monique; Matzapetakis, Manolis; Singer, David; Berger, Stefan

    2013-04-26

    Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer's disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau₂₂₉₋₂₃₇[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B₂₄₁₋₂₅₅ originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible.

  12. PEPTIDE SOLUBILITY, STRUCTURE AND CHARGE POSITION EFFECT ON ADSORPTION BY ALUMINIUM HYDROXIDE

    Directory of Open Access Journals (Sweden)

    Mary Trujillo

    2008-04-01

    Full Text Available Solubility, structure and position of charges in a peptide antigen sequence can be mentioned as being amongst the basic features of adsorption. In order to study their effect on adsorption, seven analogue series were synthesized from a MSP-1 peptide sequence by systematically replacing each one of the positions in the peptide sequence by aspartic acid, glutamic acid, serine, alanine, asparagine, glutamine or lysine. Such modifications in analogue peptide sequences showed a non-regular tendency regarding solubility and adsorption data. Aspartic acid and Glutamic acid analogue series showed great improvements in adsorption, especially in peptides where Lysine in position 6 and Arginine in position 13 were replaced. Solubility of position 5 analogue was greater than the position 6 analogue in Aspartic acid series; however, the position 6 analogue showed best adsorption results whilst the Aspartic acid in position 5 analogue showed no adsorption in the same conditions. Nuclear Magnetic Resonance structural analysis revealed differences in the -helical structureextension between these analogues. The Aspartic acid in position 6, located in the polar side of the helix, may allow this analogueto fit better onto the adsorption regions suggesting that the local electrostatic charge is responsible for this behavior.

  13. Atomic structure of a peptide coated gold nanocluster identified using theoretical and experimental studies

    Science.gov (United States)

    Wang, Hui; Li, Xu; Gao, Liang; Zhai, Jiao; Liu, Ru; Gao, Xueyun; Wang, Dongqi; Zhao, Lina

    2016-06-01

    Peptide coated gold nanoclusters (AuNCs) have a precise molecular formula and atomic structure, which are critical for their unique applications in targeting specific proteins either for protein analysis or drug design. To date, a study of the crystal structure of peptide coated AuNCs is absent primarily due to the difficulty of obtaining their crystalline phases in an experiment. Here we study a typical peptide coated AuNC (Au24Peptide8, Peptide = H2N-CCYKKKKQAGDV-COOH, Anal. Chem., 2015, 87, 2546) to figure out its atomic structure and electronic structure using a theoretical method for the first time. In this work, we identify the explicit configuration of the essential structure of Au24Peptide8, Au24(Cys-Cys)8, using density functional theory (DFT) computations and optical spectroscopic experiments, where Cys denotes cysteine without H bonded to S. As the first multidentate ligand binding AuNC, Au24(Cys-Cys)8 is characterized as a distorted Au13 core with Oh symmetry covered by two Au(Cys-Cys) and three Au3(Cys-Cys)2 staple motifs in its atomic structure. The most stable configuration of Au24(Cys-Cys)8 is confirmed by comparing its UV-vis absorption spectrum from time-dependent density-functional theory (TDDFT) calculations with optical absorption measurements, and these results are consistent with each other. Furthermore, we carry out frontier molecular orbital (FMO) calculations to elucidate that the electronic structure of Au24(Cys-Cys)8 is different from that of Au24(SR)20 as they have a different Au/S ratio, where SR represents alkylthiolate. Importantly, the different ligand coatings, Cys-Cys and SR, in Au24(Cys-Cys)8 and Au24(SR)20 cause the different Au/S ratios in the coated Au24. The reason is that the Au/S ratio is crucial in determining the size of the Au core of the ligand protected AuNC, and the size of the Au core corresponds to a specific electronic structure. By the adjustment of ligand coatings from alkylthiolate to peptide, the Au/S ratio

  14. Contribution to the study of proteins and peptides structure by hydrogen isotopic exchange

    International Nuclear Information System (INIS)

    Nabedryk-Viala, Eliane.

    1978-01-01

    Development of hydrogen exchange measurement methods to study the structure and the molecular interaction of globular protein molecules in aqueous solution (ribonuclease A, cytochrome c, coupling factors of chloroplasts), in peptide hormones in trifluoroethanol solution (angiotensin II, corticotropin) and in proteins of membranes (rhodopsin) [fr

  15. Structural properties of a peptide derived from H+-V-ATPase subunit a

    NARCIS (Netherlands)

    Vermeer, L.S.; Reat, V.; Hemminga, M.A.; Milon, A.

    2009-01-01

    The 3D structure of a peptide derived from the putative transmembrane segment 7 (TM7) of subunit a from H+-V-ATPase from Saccharomyces cerevisiae has been determined by solution state NMR in SDS. A stable helix is formed from L736 up to and including Q745, the lumenal half of the putative TM7. The

  16. Deamidation of asparagine and glutamine residues in proteins and peptides: structural determinants and analytical methodology

    NARCIS (Netherlands)

    Bischoff, Rainer; Kolbe, H.V.

    1994-01-01

    Non-enzymatic deamidation of asparagine and glutamine residues in proteins and peptides are reviewed by first outlining the well-described reaction mechanism involving cyclic imide intermediates, followed by a discussion of structural features which influence the reaction rate. The second and major

  17. Ocean acidification affects marine chemical communication by changing structure and function of peptide signalling molecules.

    Science.gov (United States)

    Roggatz, Christina C; Lorch, Mark; Hardege, Jörg D; Benoit, David M

    2016-12-01

    Ocean acidification is a global challenge that faces marine organisms in the near future with a predicted rapid drop in pH of up to 0.4 units by the end of this century. Effects of the change in ocean carbon chemistry and pH on the development, growth and fitness of marine animals are well documented. Recent evidence also suggests that a range of chemically mediated behaviours and interactions in marine fish and invertebrates will be affected. Marine animals use chemical cues, for example, to detect predators, for settlement, homing and reproduction. But, while effects of high CO 2 conditions on these behaviours are described across many species, little is known about the underlying mechanisms, particularly in invertebrates. Here, we investigate the direct influence of future oceanic pH conditions on the structure and function of three peptide signalling molecules with an interdisciplinary combination of methods. NMR spectroscopy and quantum chemical calculations were used to assess the direct molecular influence of pH on the peptide cues, and we tested the functionality of the cues in different pH conditions using behavioural bioassays with shore crabs (Carcinus maenas) as a model system. We found that peptide signalling cues are susceptible to protonation in future pH conditions, which will alter their overall charge. We also show that structure and electrostatic properties important for receptor binding differ significantly between the peptide forms present today and the protonated signalling peptides likely to be dominating in future oceans. The bioassays suggest an impaired functionality of the signalling peptides at low pH. Physiological changes due to high CO 2 conditions were found to play a less significant role in influencing the investigated behaviour. From our results, we conclude that the change of charge, structure and consequently function of signalling molecules presents one possible mechanism to explain altered behaviour under future oceanic p

  18. Structural and functional characterization of a multifunctional alanine-rich peptide analogue from Pleuronectes americanus.

    Directory of Open Access Journals (Sweden)

    Ludovico Migliolo

    Full Text Available Recently, defense peptides that are able to act against several targets have been characterized. The present work focuses on structural and functional evaluation of the peptide analogue Pa-MAP, previously isolated as an antifreeze peptide from Pleuronectes americanus. Pa-MAP showed activities against different targets such as tumoral cells in culture (CACO-2, MCF-7 and HCT-116, bacteria (Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 25923, viruses (HSV-1 and HSV-2 and fungi (Candida parapsilosis ATCC 22019, Trichophyton mentagrophytes (28d&E and T. rubrum (327. This peptide did not show toxicity against mammalian cells such as erythrocytes, Vero and RAW 264.7 cells. Molecular mechanism of action was related to hydrophobic residues, since only the terminal amino group is charged at pH 7 as confirmed by potentiometric titration. In order to shed some light on its structure-function relations, in vitro and in silico assays were carried out using circular dichroism and molecular dynamics. Furthermore, Pa-MAP showed partial unfolding of the peptide changes in a wide pH (3 to 11 and temperature (25 to 95°C ranges, although it might not reach complete unfolding at 95°C, suggesting a high conformational stability. This peptide also showed a conformational transition with a partial α-helical fold in water and a full α-helical core in SDS and TFE environments. These results were corroborated by spectral data measured at 222 nm and by 50 ns dynamic simulation. In conclusion, data reported here show that Pa-MAP is a potential candidate for drug design against pathogenic microorganisms due to its structural stability and wide activity against a range of targets.

  19. Molecular Design, Structures, and Activity of Antimicrobial Peptide-Mimetic Polymers

    Science.gov (United States)

    Takahashi, Haruko; Palermo, Edmund F.; Yasuhara, Kazuma; Caputo, Gregory A.

    2014-01-01

    There is an urgent need for new antibiotics which are effective against drug-resistant bacteria without contributing to resistance development. We have designed and developed antimicrobial copolymers with cationic amphiphilic structures based on the mimicry of naturally occurring antimicrobial peptides. These copolymers exhibit potent antimicrobial activity against a broad spectrum of bacteria including methicillin-resistant Staphylococcus aureus with no adverse hemolytic activity. Notably, these polymers also did not result in any measurable resistance development in E. coli. The peptide-mimetic design principle offers significant flexibility and diversity in the creation of new antimicrobial materials and their potential biomedical applications. PMID:23832766

  20. Mapping the antigenic structure of porcine parvovirus at the level of peptides

    DEFF Research Database (Denmark)

    Kamstrup, Søren; Langeveld, Jan; Bøtner, Anette

    1998-01-01

    The antigenic structure of the capsid proteins of porcine parvovirus (PPV) was investigated. A total of nine linear epitopes were identified by Pepscan using porcine or rabbit anti-PPV antisera. No sites were identified with a panel of neutralising monoclonal antibodies (MAbs). All epitopes were...... located in the region corresponding to the major capsid protein VP2. Based on this information, and on analogy to other autonomous parvoviruses, 24 different peptides were synthesised, coupled to keyhole limpet haemocyanin (KLH) and used to immunise rabbits. Most antisera were able to bind viral protein....... It is concluded that in PPV, the VP2 N-terminus is involved in virus neutralisation (VN) and peptides from this region are therefore primary targets for developing peptide-based vaccines against this virus....

  1. Structural and Thermodynamic Properties of Amyloid-β Peptides: Impact of Fragment Size

    Science.gov (United States)

    Kitahara, T.; Wise-Scira, O.; Coskuner, O.

    2010-10-01

    Alzheimer's disease is a progressive neurodegenerative disease whose physiological characteristics include the accumulation of amyloid-containing deposits in the brain and consequent synapse and neuron loss. Unfortunately, most widely used drugs for the treatment can palliate the outer symptoms but cannot cure the disease itself. Hence, developing a new drug that can cure it. Most recently, the ``early aggregation and monomer'' hypothesis has become popular and a few drugs have been developed based on this hypothesis. Detailed understanding of the amyloid-β peptide structure can better help us to determine more effective treatment strategies; indeed, the structure of Amyloid has been studied extensively employing experimental and theoretical tools. Nevertheless, those studies have employed different fragment sizes of Amyloid and characterized its conformational nature in different media. Thus, the structural properties might be different from each other and provide a reason for the existing debates in the literature. Here, we performed all-atom MD simulations and present the structural and thermodynamic properties of Aβ1-16, Aβ1-28, and Aβ1-42 in the gas phase and in aqueous solution. Our studies show that the overall structures, secondary structures, and the calculated thermodynamic properties change with increasing peptide size. In addition, we find that the structural properties of those peptides are different from each other in the gas phase and in aqueous solution.

  2. Toward Structure Prediction for Short Peptides Using the Improved SAAP Force Field Parameters

    Directory of Open Access Journals (Sweden)

    Kenichi Dedachi

    2013-01-01

    Full Text Available Based on the observation that Ramachandran-type potential energy surfaces of single amino acid units in water are in good agreement with statistical structures of the corresponding amino acid residues in proteins, we recently developed a new all-atom force field called SAAP, in which the total energy function for a polypeptide is expressed basically as a sum of single amino acid potentials and electrostatic and Lennard-Jones potentials between the amino acid units. In this study, the SAAP force field (SAAPFF parameters were improved, and classical canonical Monte Carlo (MC simulation was carried out for short peptide models, that is, Met-enkephalin and chignolin, at 300 K in an implicit water model. Diverse structures were reasonably obtained for Met-enkephalin, while three folded structures, one of which corresponds to a native-like structure with three native hydrogen bonds, were obtained for chignolin. The results suggested that the SAAP-MC method is useful for conformational sampling for the short peptides. A protocol of SAAP-MC simulation followed by structural clustering and examination of the obtained structures by ab initio calculation or simply by the number of the hydrogen bonds (or the hardness was demonstrated to be an effective strategy toward structure prediction for short peptide molecules.

  3. Structural similarity between β(3)-peptides synthesized from β(3)-homo-amino acids and aspartic acid monomers.

    Science.gov (United States)

    Ahmed, Sahar; Sprules, Tara; Kaur, Kamaljit

    2014-07-01

    Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β(3)-hexapeptides synthesized from L-aspartic acid monomers (β(3)-peptides 1, 5a, and 6) or homologated β(3)-amino acids (β(3)-peptide 2), fold into similar stable 14-helical secondary structures in solution, except that the former form right-handed 14-helix and the later form left-handed 14-helix. β(3)-Peptides from L-Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the NMR solution structures, we found that β(3)-peptide from L-Asp monomers (1) and from homologated amino acids (2) form similar structures with no additional side-chain interactions. These results suggest that the β(3)-peptides derived from L-Asp are promising peptide-mimetics that can be readily synthesized using L-Asp monomers as well as the right-handed 14-helical conformation of these β(3)-peptides (such as 1 and 6) may prove beneficial in the design of mimics for right-handed α-helix of α-peptides. © 2014 Wiley Periodicals, Inc.

  4. Prospects in the use of aptamers for characterizing the structure and stability of bioactive proteins and peptides in food.

    Science.gov (United States)

    Agyei, Dominic; Acquah, Caleb; Tan, Kei Xian; Hii, Hieng Kok; Rajendran, Subin R C K; Udenigwe, Chibuike C; Danquah, Michael K

    2018-01-01

    Food-derived bioactive proteins and peptides have gained acceptance among researchers, food manufacturers and consumers as health-enhancing functional food components that also serve as natural alternatives for disease prevention and/or management. Bioactivity in food proteins and peptides is determined by their conformations and binding characteristics, which in turn depend on their primary and secondary structures. To maintain their bioactivities, the molecular integrity of bioactive peptides must remain intact, and this warrants the study of peptide form and structure, ideally with robust, highly specific and sensitive techniques. Short single-stranded nucleic acids (i.e. aptamers) are known to have high affinity for cognate targets such as proteins and peptides. Aptamers can be produced cost-effectively and chemically derivatized to increase their stability and shelf life. Their improved binding characteristics and minimal modification of the target molecular signature suggests their suitability for real-time detection of conformational changes in both proteins and peptides. This review discusses the developmental progress of systematic evolution of ligands by exponential enrichment (SELEX), an iterative technology for generating cost-effective aptamers with low dissociation constants (K d ) for monitoring the form and structure of bioactive proteins and peptides. The review also presents case studies of this technique in monitoring the structural stability of bioactive peptide formulations to encourage applications in functional foods. The challenges and potential of aptamers in this research field are also discussed. Graphical abstract Advancing bioactive proteins and peptide functionality via aptameric ligands.

  5. Structural basis for phosphopantetheinyl carrier domain interactions in the terminal module of nonribosomal peptide synthetases

    Science.gov (United States)

    Liu, Ye; Zheng, Tengfei; Bruner, Steven D.

    2011-01-01

    Summary Phosphopantetheine-modified carrier domains play a central role in the template-directed, biosynthesis of several classes of primary and secondary metabolites. Fatty acids, polyketides and nonribosomal peptides are constructed on multidomain enzyme assemblies using phosphopantetheinyl thioester-linked carrier domains to traffic and activate building blocks. The carrier domain is a dynamic component of the process, shuttling pathway intermediates to sequential enzyme active sites. Here we report an approach to structurally fix carrier domain/enzyme constructs suitable for X-ray crystallographic analysis. The structure of a two-domain construct of E. coli EntF was determined with a conjugated phosphopantetheinyl-based inhibitor. The didomain structure is locked in an active orientation relevant to the chemistry of nonribosomal peptide biosynthesis. This structure provides details into the interaction of phosphopantetheine arm with the carrier domain and the active site of the thioesterase domain. PMID:22118682

  6. Structural determinants for selective recognition of peptide ligands for endothelin receptor subtypes ETA and ETB.

    Science.gov (United States)

    Lättig, Jens; Oksche, Alexander; Beyermann, Michael; Rosenthal, Walter; Krause, Gerd

    2009-07-01

    The molecular basis for recognition of peptide ligands endothelin-1, -2 and -3 in endothelin receptors is poorly understood. Especially the origin of ligand selectivity for ET(A) or ET(B) is not clearly resolved. We derived sequence-structure-function relationships of peptides and receptors from mutational data and homology modeling. Our major findings are the dissection of peptide ligands into four epitopes and the delineation of four complementary structural portions on receptor side explaining ligand recognition in both endothelin receptor subtypes. In addition, structural determinants for ligand selectivity could be described. As a result, we could improve the selectivity of BQ3020 about 10-fold by a single amino acid substitution, validating our hypothesis for ligand selectivity caused by different entrances to the receptors' transmembrane binding sites. A narrow tunnel shape in ET(A) is restrictive for a selected group of peptide ligands' N-termini, whereas a broad funnel-shaped entrance in ET(B) accepts a variety of different shapes and properties of ligands.

  7. Toxin structures as evolutionary tools: Using conserved 3D folds to study the evolution of rapidly evolving peptides.

    Science.gov (United States)

    Undheim, Eivind A B; Mobli, Mehdi; King, Glenn F

    2016-06-01

    Three-dimensional (3D) structures have been used to explore the evolution of proteins for decades, yet they have rarely been utilized to study the molecular evolution of peptides. Here, we highlight areas in which 3D structures can be particularly useful for studying the molecular evolution of peptide toxins. Although we focus our discussion on animal toxins, including one of the most widespread disulfide-rich peptide folds known, the inhibitor cystine knot, our conclusions should be widely applicable to studies of the evolution of disulfide-constrained peptides. We show that conserved 3D folds can be used to identify evolutionary links and test hypotheses regarding the evolutionary origin of peptides with extremely low sequence identity; construct accurate multiple sequence alignments; and better understand the evolutionary forces that drive the molecular evolution of peptides. Also watch the video abstract. © 2016 WILEY Periodicals, Inc.

  8. Structure-activity relationship of Trp-containing analogs of the antimicrobial peptide gomesin.

    Science.gov (United States)

    Domingues, Tatiana M; Buri, Marcus V; Daffre, Sirlei; Campana, Patricia T; Riske, Karin A; Miranda, Antonio

    2014-06-01

    Gomesin (Gm) has a broad antimicrobial activity making it of great interest for development of drugs. In this study, we analyzed three Gm analogs, [Trp(1) ]-Gm, [Trp(7) ]-Gm, and [Trp(9) ]-Gm, in an attempt to gain insight into the contributions of different regions of the peptide sequence to its activity. The incorporation of the tryptophan residue in different positions has no effect on the antimicrobial and hemolytic activities of the Gm analogs in relation to Gm. Spectroscopic studies (circular dichroism, fluorescence and absorbance) of Gm and its analogs were performed in the presence of SDS, below and above its critical micelle concentration (CMC) (~8 mM), in order to monitor structural changes induced by the interaction with this anionic surfactant (0-15 mM). Interestingly, we found that the analogs interact more strongly with SDS at low concentrations (0.3-6.0 mM) than close to or above its CMC. This suggests that SDS monomers are able to cover the whole peptide, forming large detergent-peptide aggregates. On the other hand, the peptides interact differently with SDS micelles, inserting partially into the micelle core. Among the peptides, Trp in position 1 becomes more motionally-restricted in the presence of SDS, probably because this residue is located at the N-terminal region, which presents higher conformational freedom to interact stronger with SDS molecules. Trp residues in positions 7 and 9, close to and in the region of the turn of the molecule, respectively, induced a more constrained structure and the compounds cannot insert deeper into the micelle core or be completely buried by SDS monomers. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

  9. Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin.

    Science.gov (United States)

    Hwang, P M; Zhou, N; Shan, X; Arrowsmith, C H; Vogel, H J

    1998-03-24

    The solution structure of bovine lactoferricin (LfcinB) has been determined using 2D 1H NMR spectroscopy. LfcinB is a 25-residue antimicrobial peptide released by pepsin cleavage of lactoferrin, an 80 kDa iron-binding glycoprotein with many immunologically important functions. The NMR structure of LfcinB reveals a somewhat distorted antiparallel beta-sheet. This contrasts with the X-ray structure of bovine lactoferrin, in which residues 1-13 (of LfcinB) form an alpha-helix. Hence, this region of lactoferricin B appears able to adopt a helical or sheetlike conformation, similar to what has been proposed for the amyloidogenic prion proteins and Alzheimer's beta-peptides. LfcinB has an extended hydrophobic surface comprised of residues Phe1, Cys3, Trp6, Trp8, Pro16, Ile18, and Cys20. The side chains of these residues are well-defined in the NMR structure. Many hydrophilic and positively charged residues surround the hydrophobic surface, giving LfcinB an amphipathic character. LfcinB bears numerous similarities to a vast number of cationic peptides which exert their antimicrobial activities through membrane disruption. The structures of many of these peptides have been well characterized, and models of their membrane-permeabilizing mechanisms have been proposed. The NMR solution structure of LfcinB may be more relevant to membrane interaction than that suggested by the X-ray structure of intact lactoferrin. Based on the solution structure, it is now possible to propose potential mechanisms for the antimicrobial action of LfcinB.

  10. Total synthesis, structure, and oral absorption of a thiazole cyclic peptide, sanguinamide A

    DEFF Research Database (Denmark)

    Nielsen, Daniel S; Hoang, Huy N; Lohman, Rink-Jan

    2012-01-01

    The first total synthesis and three-dimensional solution structure are reported for sanguinamide A, a thiazole-containing cyclic peptide from the sea slug H. sanguineus. Solution phase fragment synthesis, solid phase fragment assembly, and solution macrocyclization were combined to give (1) in 10......% yield. Spectral properties were identical for the natural product, requiring revision of its structure from (2) to (1). Intramolecular transannular hydrogen bonds help to bury polar atoms, which enables oral absorption from the gut....

  11. β-Boomerang Antimicrobial and Antiendotoxic Peptides: Lipidation and Disulfide Bond Effects on Activity and Structure.

    Science.gov (United States)

    Mohanram, Harini; Bhattacharjya, Surajit

    2014-04-21

    Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS)-mediated inflammations are among some of the most  prominent health issues globally. Antimicrobial peptides (AMPs) are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules.

  12. β-Boomerang Antimicrobial and Antiendotoxic Peptides: Lipidation and Disulfide Bond Effects on Activity and Structure

    Directory of Open Access Journals (Sweden)

    Harini Mohanram

    2014-04-01

    Full Text Available Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS-mediated inflammations are among some of the most  prominent health issues globally. Antimicrobial peptides (AMPs are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules.

  13. Secondary structure of cell-penetrating peptides during interaction with fungal cells.

    Science.gov (United States)

    Gong, Zifan; Ikonomova, Svetlana P; Karlsson, Amy J

    2018-03-01

    Cell-penetrating peptides (CPPs) are peptides that cross cell membranes, either alone or while carrying molecular cargo. Although their interactions with mammalian cells have been widely studied, much less is known about their interactions with fungal cells, particularly at the biophysical level. We analyzed the interactions of seven CPPs (penetratin, Pep-1, MPG, pVEC, TP-10, MAP, and cecropin B) with the fungal pathogen Candida albicans using experiments and molecular simulations. Circular dichroism (CD) of the peptides revealed a structural transition from a random coil or weak helix to an α-helix occurs for all peptides when the solvent is changed from aqueous to hydrophobic. However, CD performed in the presence of C. albicans cells showed that proximity to the cell membrane is not necessarily sufficient to induce this structural transition, as penetratin, Pep-1, and MPG did not display a structural shift in the presence of cells. Monte Carlo simulations were performed to further probe the molecular-level interaction with the cell membrane, and these simulations suggested that pVEC, TP-10, MAP, and cecropin B strongly penetrate into the hydrophobic domain of the membrane lipid bilayer, inducing a transition to an α-helical conformation. In contrast, penetratin, Pep-1 and MPG remained in the hydrophilic region without a shift in conformation. The experimental data and MC simulations combine to explain how peptide structure affects their interaction with cells and their mechanism of translocation into cells (direct translocation vs. endocytosis). Our work also highlights the utility of combining biophysical experiments, biological experiments, and molecular modeling to understand biological phenomena. © 2017 The Protein Society.

  14. Structural Polymorphism in a Self-Assembled Tri-Aromatic Peptide System.

    Science.gov (United States)

    Brown, Noam; Lei, Jiangtao; Zhan, Chendi; Shimon, Linda J W; Adler-Abramovich, Lihi; Wei, Guanghong; Gazit, Ehud

    2018-04-24

    Self-assembly is a process of key importance in natural systems and in nanotechnology. Peptides are attractive building blocks due to their relative facile synthesis, biocompatibility, and other unique properties. Diphenylalanine (FF) and its derivatives are known to form nanostructures of various architectures and interesting and varied characteristics. The larger triphenylalanine peptide (FFF) was found to self-assemble as efficiently as FF, forming related but distinct architectures of plate-like and spherical nanostructures. Here, to understand the effect of triaromatic systems on the self-assembly process, we examined carboxybenzyl-protected diphenylalanine (z-FF) as a minimal model for such an arrangement. We explored different self-assembly conditions by changing solvent compositions and peptide concentrations, generating a phase diagram for the assemblies. We discovered that z-FF can form a variety of structures, including nanowires, fibers, nanospheres, and nanotoroids, the latter were previously observed only in considerably larger or co-assembly systems. Secondary structure analysis revealed that all assemblies possessed a β-sheet conformation. Additionally, in solvent combinations with high water ratios, z-FF formed rigid and self-healing hydrogels. X-ray crystallography revealed a "wishbone" structure, in which z-FF dimers are linked by hydrogen bonds mediated by methanol molecules, with a 2-fold screw symmetry along the c-axis. All-atom molecular dynamics (MD) simulations revealed conformations similar to the crystal structure. Coarse-grained MD simulated the assembly of the peptide into either fibers or spheres in different solvent systems, consistent with the experimental results. This work thus expands the building block library for the fabrication of nanostructures by peptide self-assembly.

  15. NMR structural studies of peptides and proteins in membranes

    Energy Technology Data Exchange (ETDEWEB)

    Opella, S J [Pennsylvania Univ., Philadelphia, PA (United States). Dept. of Chemistry

    1994-12-31

    The use of NMR methodology in structural studies is described as applicable to larger proteins, considering that the majority of membrane proteins is constructed from a limited repertoire of structural and dynamic elements. The membrane associated domains of these proteins are made up of long hydrophobic membrane spanning helices, shorter amphipathic bridging helices in the plane of the bilayer, connecting loops with varying degrees of mobility, and mobile N- and C- terminal sections. NMR studies have been successful in identifying all of these elements and their orientations relative to each other and the membrane bilayer 19 refs., 9 figs.

  16. Comprehensive Peptide Ion Structure Studies Using Ion Mobility Techniques: Part 3. Relating Solution-Phase to Gas-Phase Structures.

    Science.gov (United States)

    Kondalaji, Samaneh Ghassabi; Khakinejad, Mahdiar; Valentine, Stephen J

    2018-06-01

    Molecular dynamics (MD) simulations have been utilized to study peptide ion conformer establishment during the electrospray process. An explicit water model is used for nanodroplets containing a model peptide and hydronium ions. Simulations are conducted at 300 K for two different peptide ion charge configurations and for droplets containing varying numbers of hydronium ions. For all conditions, modeling has been performed until production of the gas-phase ions and the resultant conformers have been compared to proposed gas-phase structures. The latter species were obtained from previous studies in which in silico candidate structures were filtered according to ion mobility and hydrogen-deuterium exchange (HDX) reactivity matches. Results from the present study present three key findings namely (1) the evidence from ion production modeling supports previous structure refinement studies based on mobility and HDX reactivity matching, (2) the modeling of the electrospray process is significantly improved by utilizing initial droplets existing below but close to the calculated Rayleigh limit, and (3) peptide ions in the nanodroplets sample significantly different conformers than those in the bulk solution due to altered physicochemical properties of the solvent. Graphical Abstract ᅟ.

  17. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae [Yonsei University, Seoul (Korea, Republic of)

    2012-02-15

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ{sup PEP}) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ{sup PEP} formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ{sup PEP}. The solution structure of FTZ{sup PEP} in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix.

  18. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    International Nuclear Information System (INIS)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae

    2012-01-01

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ PEP ) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ PEP formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ PEP . The solution structure of FTZ PEP in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix

  19. Structured pathway across the transition state for peptide folding revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Lipi Thukral

    2011-09-01

    Full Text Available Small globular proteins and peptides commonly exhibit two-state folding kinetics in which the rate limiting step of folding is the surmounting of a single free energy barrier at the transition state (TS separating the folded and the unfolded states. An intriguing question is whether the polypeptide chain reaches, and leaves, the TS by completely random fluctuations, or whether there is a directed, stepwise process. Here, the folding TS of a 15-residue β-hairpin peptide, Peptide 1, is characterized using independent 2.5 μs-long unbiased atomistic molecular dynamics (MD simulations (a total of 15 μs. The trajectories were started from fully unfolded structures. Multiple (spontaneous folding events to the NMR-derived conformation are observed, allowing both structural and dynamical characterization of the folding TS. A common loop-like topology is observed in all the TS structures with native end-to-end and turn contacts, while the central segments of the strands are not in contact. Non-native sidechain contacts are present in the TS between the only tryptophan (W11 and the turn region (P7-G9. Prior to the TS the turn is found to be already locked by the W11 sidechain, while the ends are apart. Once the ends have also come into contact, the TS is reached. Finally, along the reactive folding paths the cooperative loss of the W11 non-native contacts and the formation of the central inter-strand native contacts lead to the peptide rapidly proceeding from the TS to the native state. The present results indicate a directed stepwise process to folding the peptide.

  20. Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity.

    Science.gov (United States)

    Lai, Alex L; Park, Heather; White, Judith M; Tamm, Lukas K

    2006-03-03

    The fusion peptide of influenza hemagglutinin is crucial for cell entry of this virus. Previous studies showed that this peptide adopts a boomerang-shaped structure in lipid model membranes at the pH of membrane fusion. To examine the role of the boomerang in fusion, we changed several residues proposed to stabilize the kink in this structure and measured fusion. Among these, mutants E11A and W14A expressed hemagglutinins with hemifusion and no fusion activities, and F9A and N12A had no effect on fusion, respectively. Binding enthalpies and free energies of mutant peptides to model membranes and their ability to perturb lipid bilayer structures correlated well with the fusion activities of the parent full-length molecules. The structure of W14A determined by NMR and site-directed spin labeling features a flexible kink that points out of the membrane, in sharp contrast to the more ordered boomerang of the wild-type, which points into the membrane. A specific fixed angle boomerang structure is thus required to support membrane fusion.

  1. Structure and dynamics of the peptide strand KRFK from the thrombospondin TSP-1 in water.

    Science.gov (United States)

    Taleb Bendiab, W; Benomrane, B; Bounaceur, B; Dauchez, M; Krallafa, A M

    2018-02-14

    Theoretical investigations of a solute in liquid water at normal temperature and pressure can be performed at different levels of theory. Static quantum calculations as well as classical and ab initio molecular dynamics are used to completely explore the conformational space for large solvated molecular systems. In the classical approach, it is essential to describe all of the interactions of the solute and the solvent in detail. Water molecules are very often described as rigid bodies when the most commonly used interaction potentials, such as the SPCE and the TIP4P models, are employed. Recently, a physical model based upon a cluster of rigid water molecules with a tetrahedral architecture (AB 4 ) was proposed that describes liquid water as a mixture of both TIP4P and SPCE molecular species that occur in the proportions implied by the tetrahedral architecture (one central molecule versus four outer molecules; i.e., 20% TIP4P versus 80% SPCE molecules). In this work, theoretical spectroscopic data for a peptide strand were correlated with the structural properties of the peptide strand solvated in water, based on data calculated using different theoretical approaches and physical models. We focused on a particular peptide strand, KRFK (lysine-arginine-phenylalanine-lysine), found in the thrombospondin TSP-1, due to its interesting properties. As the activity and electronic structure of this system is strongly linked to its structure, we correlated its structure with charge-density maps obtained using different semi-empirical charge Q eq equations. The structural and thermodynamic properties obtained from classical simulations were correlated with ab initio molecular dynamics (AIMD) data. Structural changes in the peptide strand were rationalized in terms of the motions of atoms and groups of atoms. To achieve this, conformational changes were investigated using calculated infrared spectra for the peptide in the gas phase and in water solvent. The calculated AIMD

  2. Structures of self-assembled amphiphilic peptide-heterodimers: effects of concentration, pH, temperature and ionic strength

    KAUST Repository

    Luo, Zhongli; Å kerman, Bjö rn; Zhang, Shuguang; Nordé n, Bengt

    2010-01-01

    -studies indicate that the NaCl has only a minor effect on the peptide secondary structure we propose that the main role of the added salt is to screen the electrostatic repulsion between the peptide building blocks. According to the AFM images ADG and AKG support a

  3. Identifying Residual Structure in Intrinsically Disordered Systems : A 2D IR Spectroscopic Study of the GVGXPGVG Peptide

    NARCIS (Netherlands)

    Lessing, Joshua; Roy, Santanu; Reppert, Mike; Baer, Marcel; Marx, Dominik; Jansen, Thomas La Cour; Knoester, Jasper; Tokmakoff, Andrei

    2012-01-01

    The peptide amide-I vibration of a proline turn encodes information on the turn structure. In this study, FTIR, two-dimensional IR spectroscopy and molecular dynamics simulations were employed to characterize the varying turn conformations that exist in the GVGX(L)PGVG family of disordered peptides.

  4. Identifying residual structure in intrinsically disordered systems: a 2D IR spectroscopic study of the GVGXPGVG peptide.

    NARCIS (Netherlands)

    Lessing, J.; Roy, S.; Reppert, M.; Baer, M.; Marx, D.; Jansen, T.L.Th.A.; Knoester, J.; Tokmakoff, A.

    2012-01-01

    The peptide amide-I vibration of a proline turn encodes information on the turn structure. In this study, FTIR, two-dimensional IR spectroscopy and molecular dynamics simulations were employed to characterize the varying turn conformations that exist in the GVGX(L)PGVG family of disordered peptides.

  5. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Gao X

    2015-11-01

    Full Text Available Xiang Gao,1,2,* Xiaohong Zhang,3,* Jinlin Song,1,2 Xiao Xu,4 Anxiu Xu,1 Mengke Wang,4 Bingwu Xie,1 Enyi Huang,2 Feng Deng,1,2 Shicheng Wei2–41College of Stomatology, 2Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, 3Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, 4Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China*These authors contributed equally to this workAbstract: The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than

  6. Kinetic and structural characterization of amyloid-β peptide hydrolysis by human angiotensin-1-converting enzyme.

    Science.gov (United States)

    Larmuth, Kate M; Masuyer, Geoffrey; Douglas, Ross G; Schwager, Sylva L; Acharya, K Ravi; Sturrock, Edward D

    2016-03-01

    Angiotensin-1-converting enzyme (ACE), a zinc metallopeptidase, consists of two homologous catalytic domains (N and C) with different substrate specificities. Here we report kinetic parameters of five different forms of human ACE with various amyloid beta (Aβ) substrates together with high resolution crystal structures of the N-domain in complex with Aβ fragments. For the physiological Aβ(1-16) peptide, a novel ACE cleavage site was found at His14-Gln15. Furthermore, Aβ(1-16) was preferentially cleaved by the individual N-domain; however, the presence of an inactive C-domain in full-length somatic ACE (sACE) greatly reduced enzyme activity and affected apparent selectivity. Two fluorogenic substrates, Aβ(4-10)Q and Aβ(4-10)Y, underwent endoproteolytic cleavage at the Asp7-Ser8 bond with all ACE constructs showing greater catalytic efficiency for Aβ(4-10)Y. Surprisingly, in contrast to Aβ(1-16) and Aβ(4-10)Q, sACE showed positive domain cooperativity and the double C-domain (CC-sACE) construct no cooperativity towards Aβ(4-10)Y. The structures of the Aβ peptide-ACE complexes revealed a common mode of peptide binding for both domains which principally targets the C-terminal P2' position to the S2' pocket and recognizes the main chain of the P1' peptide. It is likely that N-domain selectivity for the amyloid peptide is conferred through the N-domain specific S2' residue Thr358. Additionally, the N-domain can accommodate larger substrates through movement of the N-terminal helices, as suggested by the disorder of the hinge region in the crystal structures. Our findings are important for the design of domain selective inhibitors as the differences in domain selectivity are more pronounced with the truncated domains compared to the more physiological full-length forms. The atomic coordinates and structure factors for N-domain ACE with Aβ peptides 4-10 (5AM8), 10-16 (5AM9), 1-16 (5AMA), 35-42 (5AMB) and (4-10)Y (5AMC) complexes have been deposited in the

  7. Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

    Energy Technology Data Exchange (ETDEWEB)

    Misono, K. S.; Philo, J. S.; Arakawa, T.; Ogata, C. M.; Qiu, Y.; Ogawa, H.; Young, H. S. (Biosciences Division); (Univ. of Nevada); (Alliance Protein Labs.)

    2011-06-01

    Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.

  8. Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure.

    Science.gov (United States)

    Wu, Alan H B; Smith, Andrew

    2004-03-15

    B-type natriuretic peptide (BNP) and the inactive metabolite NT-proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8-week biological variability (BV) of BNP and NT-proBNP assays in healthy subjects and the 1-day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence). We applied the biological variability concepts to the serial results of BNP and NT-proBNP collected from patients with heart failure and compared the performance of these two markers. While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value. Frequent testing (e.g. daily) for BNP and NT-proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.

  9. Bats aloft: Variation in echolocation call structure at high altitudes

    Science.gov (United States)

    Bats alter their echolocation calls in response to changes in ecological and behavioral conditions, but little is known about how they adjust their call structure in response to changes in altitude. This study examines altitudinal variation in the echolocation calls of Brazilian free-tailed bats, T...

  10. Variational cellular model of the molecular and crystal electronic structure

    International Nuclear Information System (INIS)

    Ferreira, L.G.; Leite, J.R.

    1977-12-01

    A variational version of the cellular method is developed to calculate the electronic structure of molecules and crystals. Due to the simplicity of the secular equation, the method is easy to be implemented. Preliminary calculations on the hydrogen molecular ion suggest that it is also accurate and of fast convergence [pt

  11. Conservation of Three-Dimensional Helix-Loop-Helix Structure through the Vertebrate Lineage Reopens the Cold Case of Gonadotropin-Releasing Hormone-Associated Peptide.

    Science.gov (United States)

    Pérez Sirkin, Daniela I; Lafont, Anne-Gaëlle; Kamech, Nédia; Somoza, Gustavo M; Vissio, Paula G; Dufour, Sylvie

    2017-01-01

    GnRH-associated peptide (GAP) is the C-terminal portion of the gonadotropin-releasing hormone (GnRH) preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide only participates in the folding or carrying process of GnRH. Considering that the three-dimensional (3D) structure of a protein may define its function, the aim of this study was to evaluate if GAP sequences and 3D structures are conserved in the vertebrate lineage. GAP sequences from various vertebrates were retrieved from databases. Analysis of primary amino acid sequence identity and similarity, molecular phylogeny, and prediction of 3D structures were performed. Amino acid sequence comparison and phylogeny analyses confirmed the large variation of GAP sequences throughout vertebrate radiation. In contrast, prediction of the 3D structure revealed a striking conservation of the 3D structure of GAP1 (GAP associated with the hypophysiotropic type 1 GnRH), despite low amino acid sequence conservation. This GAP1 peptide presented a typical helix-loop-helix (HLH) structure in all the vertebrate species analyzed. This HLH structure could also be predicted for GAP2 in some but not all vertebrate species and in none of the GAP3 analyzed. These results allowed us to infer that selective pressures have maintained GAP1 HLH structure throughout the vertebrate lineage. The conservation of the HLH motif, known to confer biological activity to various proteins, suggests that GAP1 peptides may exert some hypophysiotropic biological functions across vertebrate radiation.

  12. Conservation of Three-Dimensional Helix-Loop-Helix Structure through the Vertebrate Lineage Reopens the Cold Case of Gonadotropin-Releasing Hormone-Associated Peptide

    Directory of Open Access Journals (Sweden)

    Daniela I. Pérez Sirkin

    2017-08-01

    Full Text Available GnRH-associated peptide (GAP is the C-terminal portion of the gonadotropin-releasing hormone (GnRH preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide only participates in the folding or carrying process of GnRH. Considering that the three-dimensional (3D structure of a protein may define its function, the aim of this study was to evaluate if GAP sequences and 3D structures are conserved in the vertebrate lineage. GAP sequences from various vertebrates were retrieved from databases. Analysis of primary amino acid sequence identity and similarity, molecular phylogeny, and prediction of 3D structures were performed. Amino acid sequence comparison and phylogeny analyses confirmed the large variation of GAP sequences throughout vertebrate radiation. In contrast, prediction of the 3D structure revealed a striking conservation of the 3D structure of GAP1 (GAP associated with the hypophysiotropic type 1 GnRH, despite low amino acid sequence conservation. This GAP1 peptide presented a typical helix-loop-helix (HLH structure in all the vertebrate species analyzed. This HLH structure could also be predicted for GAP2 in some but not all vertebrate species and in none of the GAP3 analyzed. These results allowed us to infer that selective pressures have maintained GAP1 HLH structure throughout the vertebrate lineage. The conservation of the HLH motif, known to confer biological activity to various proteins, suggests that GAP1 peptides may exert some hypophysiotropic biological functions across vertebrate radiation.

  13. Probabilistic frequency variations of structure-soil systems

    International Nuclear Information System (INIS)

    Hamilton, C.W.; Hadjian, A.H.

    1976-01-01

    During earthquakes, structure-soil systems act as filters greatly amplifying the response of equipment whose frequencies are at or near their natural frequencies. Thus, the estimation of these structure-soil system frequencies assumes significant importance both for safety and cost. Actual in-situ frequencies of structures differ from calculated frequencies due both to variations in mathematical modelling techniques and to variations of material properties. This paper studies the second source only. This variability is usually gauged by the 'worst case' analyses technique in which extreme high- and low- parameter values are assumed and the associated frequencies are used as upper and lower bounds. This approach is not entirely satisfactory because it does not provide any indication of the probability of these limits being exceeded, of the distribution between these limits, or of the level of conservation introduced into the design process. The present approach provides this additional information. The emphasis in this part is both on developing the methodology and on the results obtained. It covers both the fixed-base structure and the effects of soil-structure interaction. Empirical data on concrete proerties were obtained from previously published results. Much less is known about variability of soil properties, so the soil structure interaction coefficients are assumed to be normally distributed. As data on the variation of soil properties become available, they can be readily incorporated via the methodology developed here. (Auth.)

  14. Structural Study of a New HIV-1 Entry Inhibitor and Interaction with the HIV-1 Fusion Peptide in Dodecylphosphocholine Micelles.

    Science.gov (United States)

    Pérez, Yolanda; Gómara, Maria José; Yuste, Eloísa; Gómez-Gutierrez, Patricia; Pérez, Juan Jesús; Haro, Isabel

    2017-08-25

    Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Structural variations and physical properties of lignin coke

    International Nuclear Information System (INIS)

    Otani, C.

    1986-01-01

    The studied lignin is a by-product of the process of ethanol production from eucaliptus. It was heat-treated under inert atmosphere conditions at increasing temperatures from 300 0 C up to 2600 0 C. This material has about 35 weight % of carbon yield and low ash content (0.70 w %). The structural variations were studied by wide-angle X-ray diffraction, small-angle X-ray scattering and infra-red spectroscopy. The bulk and the ''real'' density of the samples have also been determined as a function of the heat treatment temperatures. These experimental results enabled us to establish a mechanism of structure variation based on the formation of a graphite-like and porous structure within the initially amorphous lignin matrix. It has been possible to specify the adequate heat treatment temperature based upon the lignin coke applications. (author) [pt

  16. New Tests for Variations of the Fine Structure Constant

    Science.gov (United States)

    Prestage, John D.

    1995-01-01

    We describe a new test for possible variations of the fine structure constant, by comparisons of rates between clocks based on hyperfine transitions in alkali atomos with different atomic number Z. H- maser, Cs and Hg+ clocks have a different dependence on ia relativistic contributions of order (Z. Recent H-maser vs Hg+ clock comparison data improves laboratory limits on a time variation by 100-fold to giveFuture laser cooled clocks (Be+, Rb, Cs, Hg+, etc.), when compared, will yield the most senstive of all tests for.

  17. Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.

    Science.gov (United States)

    Runge, Steffen; Thøgersen, Henning; Madsen, Kjeld; Lau, Jesper; Rudolph, Rainer

    2008-04-25

    The glucagon-like peptide-1 receptor (GLP-1R) belongs to Family B1 of the seven-transmembrane G protein-coupled receptors, and its natural agonist ligand is the peptide hormone glucagon-like peptide-1 (GLP-1). GLP-1 is involved in glucose homeostasis, and activation of GLP-1R in the plasma membrane of pancreatic beta-cells potentiates glucose-dependent insulin secretion. The N-terminal extracellular domain (nGLP-1R) is an important ligand binding domain that binds GLP-1 and the homologous peptide Exendin-4 with differential affinity. Exendin-4 has a C-terminal extension of nine amino acid residues known as the "Trp cage", which is absent in GLP-1. The Trp cage was believed to interact with nGLP-1R and thereby explain the superior affinity of Exendin-4. However, the molecular details that govern ligand binding and specificity of nGLP-1R remain undefined. Here we report the crystal structure of human nGLP-1R in complex with the antagonist Exendin-4(9-39) solved by the multiwavelength anomalous dispersion method to 2.2A resolution. The structure reveals that Exendin-4(9-39) is an amphipathic alpha-helix forming both hydrophobic and hydrophilic interactions with nGLP-1R. The Trp cage of Exendin-4 is not involved in binding to nGLP-1R. The hydrophobic binding site of nGLP-1R is defined by discontinuous segments including primarily a well defined alpha-helix in the N terminus of nGLP-1R and a loop between two antiparallel beta-strands. The structure provides for the first time detailed molecular insight into ligand binding of the human GLP-1 receptor, an established target for treatment of type 2 diabetes.

  18. Structures of self-assembled amphiphilic peptide-heterodimers: effects of concentration, pH, temperature and ionic strength

    KAUST Repository

    Luo, Zhongli

    2010-01-01

    The amphiphilic double-tail peptides AXG were studied regarding secondary structure and self-assembly in aqueous solution. The two tails A = Ala 6 and G = Gly6 are connected by a central pair X of hydrophilic residues, X being two aspartic acids in ADG, two lysines in AKG and two arginines in ARG. The peptide AD (Ala6Asp) served as a single-tail reference. The secondary structure of the four peptides was characterized by circular dichroism spectroscopy under a wide range of peptide concentrations (0.01-0.8 mM), temperatures (20-98 °C), pHs (4-9.5) and ionic strengths. In salt-free water both ADG and AD form a β-sheet type of structure at high concentration, low pH and low temperature, in a peptide-peptide driven assembly of individual peptides. The transition has a two-state character for ADG but not for AD, which indicates that the added tail in ADG makes the assembly more cooperative. By comparison the secondary structures of AKG and ARG are comparatively stable over the large range of conditions covered. According to dynamic light scattering the two-tail peptides form supra-molecular aggregates in water, but high-resolution AFM-imaging indicate that ordered (self-assembled) structures are only formed when salt (0.1 M NaCl) is added. Since the CD-studies indicate that the NaCl has only a minor effect on the peptide secondary structure we propose that the main role of the added salt is to screen the electrostatic repulsion between the peptide building blocks. According to the AFM images ADG and AKG support a correlation between nanofibers and a β-sheet or unordered secondary structure, whereas ARG forms fibers in spite of lacking β-sheet structure. Since the AKG and ARG double-tail peptides self-assemble into distinct nanostructures while their secondary structures are resistant to environment factors, these new peptides show potential as robust building blocks for nano-materials in various medical and nanobiotechnical applications. © 2010 The Royal Society

  19. Time variation of the fine structure constant driven by quintessence

    International Nuclear Information System (INIS)

    Anchordoqui, Luis; Goldberg, Haim

    2003-01-01

    There are indications from the study of quasar absorption spectra that the fine structure constant α may have been measurably smaller for redshifts z>2. Analyses of other data ( 149 Sm fission rate for the Oklo natural reactor, variation of 187 Re β-decay rate in meteorite studies, atomic clock measurements) which probe variations of α in the more recent past imply much smaller deviations from its present value. In this work we tie the variation of α to the evolution of the quintessence field proposed by Albrecht and Skordis, and show that agreement with all these data, as well as consistency with Wilkinson Microwave Anisotropy Probe observations, can be achieved for a range of parameters. Some definite predictions follow for upcoming space missions searching for violations of the equivalence principle

  20. Antimicrobial Peptides from Plants

    Directory of Open Access Journals (Sweden)

    James P. Tam

    2015-11-01

    Full Text Available Plant antimicrobial peptides (AMPs have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic, lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.

  1. Polymorphism of fibrillar structures depending on the size of assembled Aβ17-42 peptides

    Science.gov (United States)

    Cheon, Mookyung; Kang, Mooseok; Chang, Iksoo

    2016-01-01

    The size of assembled Aβ17-42 peptides can determine polymorphism during oligomerization and fibrillization, but the mechanism of this effect is unknown. Starting from separate random monomers, various fibrillar oligomers with distinct structural characteristics were identified using discontinuous molecular dynamics simulations based on a coarse-grained protein model. From the structures observed in the simulations, two characteristic oligomer sizes emerged, trimer and paranuclei, which generated distinct structural patterns during fibrillization. A majority of the simulations for trimers and tetramers formed non-fibrillar oligomers, which primarily progress to off-pathway oligomers. Pentamers and hexamers were significantly converted into U-shape fibrillar structures, meaning that these oligomers, called paranuclei, might be potent on-pathway intermediates in fibril formation. Fibrillar oligomers larger than hexamers generated substantial polymorphism in which hybrid structures were readily formed and homogeneous fibrillar structures appeared infrequently. PMID:27901087

  2. Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.

    Science.gov (United States)

    Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

    2015-11-01

    Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity. However, the addition of the repeat (di-peptide) and the retro-repeat (di-retro-peptide) sequences highly improved cancer cell toxicity up to 100% at 20 μM peptide concentration. Compared to the complete parent sequence hLFcin the derivatives showed toxicity on the melanoma cell line A375 increased by 10-fold and on the glioblastoma cell line U-87mg by 2-3-fold. Reduced killing velocity, apoptotic blebbing, activation of caspase 3/7 and formation of apoptotic DNA fragments proved that the active and cancer selective peptides, e.g. R-DIM-P-LF11-322, trigger apoptosis, whereas highly active, though non-selective peptides, such as DIM-LF11-318 and RW-AH seem to kill rapidly via necrosis inducing membrane lyses. Structural studies revealed specific toxicity on cancer cells by peptide derivatives with loop structures, whereas non-specific peptides comprised α-helical structures without loop. Model studies with the cancer membrane mimic phosphatidylserine (PS) gave strong evidence that PS only exposed by cancer cells is an important target for specific hLFcin derivatives. Other negatively charged membrane exposed molecules as sialic acid, heparan and chondroitin sulfate were shown to have minor impact on peptide activity. Copyright © 2015. Published by Elsevier B.V.

  3. Impact of the antimicrobial peptide Novicidin on membrane structure and integrity

    DEFF Research Database (Denmark)

    Nielsen, Søren B; Otzen, Daniel Erik

    2010-01-01

    We have studied the impact of an 18-residue cationic antimicrobial peptide Novicidin (Nc) on the structure and integrity of partially anionic lipid membranes using oriented circular dichroism (OCD), quartz crystal microbalance with dissipation (QCM-D), dual polarization interferometry (DPI......), calcein dye leakage and fluorescence spectroscopy. OCD consistently showed that Nc is bound in an alpha-helical, surface bound state over a range of peptide to lipid (P/L) ratios up to approximately 1:15. Realignment of Nc at higher P/L ratios correlates to loss of membrane integrity as shown by Laurdan...... concentration, probably through formation of transient pores or transient disruption of the membrane integrity, followed by more extensive membrane disintegration at higher P/L ratios....

  4. Genomics technologies to study structural variations in the grapevine genome

    Directory of Open Access Journals (Sweden)

    Cardone Maria Francesca

    2016-01-01

    Full Text Available Grapevine is one of the most important crop plants in the world. Recently there was great expansion of genomics resources about grapevine genome, thus providing increasing efforts for molecular breeding. Current cultivars display a great level of inter-specific differentiation that needs to be investigated to reach a comprehensive understanding of the genetic basis of phenotypic differences, and to find responsible genes selected by cross breeding programs. While there have been significant advances in resolving the pattern and nature of single nucleotide polymorphisms (SNPs on plant genomes, few data are available on copy number variation (CNV. Furthermore association between structural variations and phenotypes has been described in only a few cases. We combined high throughput biotechnologies and bioinformatics tools, to reveal the first inter-varietal atlas of structural variation (SV for the grapevine genome. We sequenced and compared four table grape cultivars with the Pinot noir inbred line PN40024 genome as the reference. We detected roughly 8% of the grapevine genome affected by genomic variations. Taken into account phenotypic differences existing among the studied varieties we performed comparison of SVs among them and the reference and next we performed an in-depth analysis of gene content of polymorphic regions. This allowed us to identify genes showing differences in copy number as putative functional candidates for important traits in grapevine cultivation.

  5. Review: evolution of GnIH and related peptides structure and function in the chordates.

    Science.gov (United States)

    Osugi, Tomohiro; Ubuka, Takayoshi; Tsutsui, Kazuyoshi

    2014-01-01

    Discovery of gonadotropin-inhibitory hormone (GnIH) in the Japanese quail in 2000 was the first to demonstrate the existence of a hypothalamic neuropeptide inhibiting gonadotropin release. We now know that GnIH regulates reproduction by inhibiting gonadotropin synthesis and release via action on the gonadotropin-releasing hormone (GnRH) system and the gonadotrope in various vertebrates. GnIH peptides identified in birds and mammals have a common LPXRF-amide (X = L or Q) motif at the C-terminus and inhibit pituitary gonadotropin secretion. However, the function and structure of GnIH peptides are diverse in fish. Goldfish GnIHs possessing a C-terminal LPXRF-amide motif have both stimulatory and inhibitory effects on gonadotropin synthesis or release. The C-terminal sequence of grass puffer and medaka GnIHs are MPQRF-amide. To investigate the evolutionary origin of GnIH and its ancestral structure and function, we searched for GnIH in agnathans, the most ancient lineage of vertebrates. We identified GnIH precursor gene and mature GnIH peptides with C-terminal QPQRF-amide or RPQRF-amide from the brain of sea lamprey. Lamprey GnIH fibers were in close proximity to GnRH-III neurons. Further, one of lamprey GnIHs stimulated the expression of lamprey GnRH-III peptide in the hypothalamus and gonadotropic hormone β mRNA expression in the pituitary. We further identified the ancestral form of GnIH, which had a C-terminal RPQRF-amide, and its receptors in amphioxus, the most basal chordate species. The amphioxus GnIH inhibited cAMP signaling in vitro. In sum, the original forms of GnIH may date back to the time of the emergence of early chordates. GnIH peptides may have had various C-terminal structures slightly different from LPXRF-amide in basal chordates, which had stimulatory and/or inhibitory functions on reproduction. The C-terminal LPXRF-amide structure and its inhibitory function on reproduction may be selected in later-evolved vertebrates, such as birds and mammals.

  6. The variational method in the atomic structure calcularion

    International Nuclear Information System (INIS)

    Tomimura, A.

    1970-01-01

    The importance and limitations of variational methods on the atomic structure calculations is set into relevance. Comparisons are made to the Perturbation Theory. Ilustrating it, the method is applied to the H - , H + and H + 2 simple atomic structure systems, and the results are analysed with basis on the study of the associated essential eigenvalue spectrum. Hydrogenic functions (where the screening constants are replaced by variational parameters) are combined to construct the wave function with proper symmetry for each one of the systems. This shows the existence of a bound state for H - , but no conclusions can be made for the others, where it may or may not be necessary to use more flexible wave functions, i.e., with greater number of terms and parameters. (author) [pt

  7. Impact of soil-structure interaction on the probabilistic frequency variation of concrete structures

    International Nuclear Information System (INIS)

    Hadjian, A.H.; Hamilton, C.W.

    1975-01-01

    Earthquake response of equipment in nuclear power plants is characterized by floor response spectra. Since these spectra peak at the natural frequencies of the structure, it is important, both from safety and cost standpoints, to determine the degree of the expected variability of the calculated structural frequencies. A previous work is extended on the variability of the natural frequencies of structures due to the variations of concrete properties and a rigorous approach is presented to evaluate frequency variations based on the probability distributions of both the structural and soil parameters and jointly determine the distributions of the natural frequencies. It is assumed that the soil-structure interaction coefficients are normally distributed. With the proper choice of coordinates, the simultaneous random variations of both the structural properties and the interaction coefficients can be incorporated in the eigenvalue problem. The key methodology problem is to obtain the probability distribution of eigenvalues of matrices with random variable elements. Since no analytic relation exists between the eigenvalues and the elements, a numerical procedure had to be designed. It was found that the desired accuracy can be best achieved by splitting the joint variation into two parts: the marginal distribution of soil variations and the conditional distribution of structural variations at specific soil fractiles. Then after calculating the actual eigenvalues at judiciously selected paired values of soil and structure parameters, this information is recombined to obtain the desired cumulative distribution of natural frequencies

  8. On the Sensitivity of Peptide Nucleic Acid Duplex Formation and Crystal Dissolution to a Variation of Force-Field Parameters.

    Science.gov (United States)

    Bachmann, Stephan J; Lin, Zhixiong; Stafforst, Thorsten; van Gunsteren, Wilfred F; Dolenc, Jožica

    2014-01-14

    The technique of one-step perturbation to explore the relation between particular force-field parameters on the one hand and particular properties of a biomolecular system on the other hand from one or a few molecular dynamics simulations is applied to investigate the dependence of the free enthalpy of dimer formation and of crystal dissolution of a self-complementary fragment (H-CGTACG-NH2) of peptide nucleic acid, PNA, a mimic of DNA. The simulations show that PNA dimer formation in aqueous solution is favored by a decrease in the base charges with respect to values of the GROMOS 45A4 force field, while it is disfavored by a decrease in the backbone charges. In contrast, crystal dissolution of the PNA dimer is favored by a decrease in base charges, while a variation of backbone charges has a minor effect on this free enthalpy change. These opposite effects in a crystalline versus aqueous solution environment can be understood from the different water contents for these systems and have consequences for biomolecular force-field development.

  9. Dissociation Behavior of a TEMPO-Active Ester Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS) in Negative ESI-MS.

    Science.gov (United States)

    Hage, Christoph; Ihling, Christian H; Götze, Michael; Schäfer, Mathias; Sinz, Andrea

    2017-01-01

    We have synthesized a homobifunctional amine-reactive cross-linking reagent, containing a TEMPO (2,2,6,6-tetramethylpiperidine-1-oxy) and a benzyl group (Bz), termed TEMPO-Bz-linker, to derive three-dimensional structural information of proteins. The aim for designing this novel cross-linker was to facilitate the mass spectrometric analysis of cross-linked products by free radical initiated peptide sequencing (FRIPS). In an initial study, we had investigated the fragmentation behavior of TEMPO-Bz-derivatized peptides upon collision activation in (+)-electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MS/MS) experiments. In addition to the homolytic NO-C bond cleavage FRIPS pathway delivering the desired odd-electron product ions, an alternative heterolytic NO-C bond cleavage, resulting in even-electron product ions mechanism was found to be relevant. The latter fragmentation route clearly depends on the protonation of the TEMPO-Bz-moiety itself, which motivated us to conduct (-)-ESI-MS, CID-MS/MS, and MS 3 experiments of TEMPO-Bz-cross-linked peptides to further clarify the fragmentation behavior of TEMPO-Bz-peptide molecular ions. We show that the TEMPO-Bz-linker is highly beneficial for conducting FRIPS in negative ionization mode as the desired homolytic cleavage of the NO-C bond is the major fragmentation pathway. Based on characteristic fragments, the isomeric amino acids leucine and isoleucine could be discriminated. Interestingly, we observed pronounced amino acid side chain losses in cross-linked peptides if the cross-linked peptides contain a high number of acidic amino acids. Graphical Abstract ᅟ.

  10. Investigation of Self-assembly Structure and Properties of a Novel Designed Lego-type Peptide with Double Amphiphilic Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Liang [Sichuan University, Sichuan (China); Zhao, Xiao Jun [Massachusetts Institute of Technology, Cambridge (United States)

    2010-12-15

    A typically designed 'Peptide Lego' has two distinct surfaces: a hydrophilic side that contains the complete charge distribution and a hydrophobic side. In this article, we describe the fabrication of a unique lego-type peptide with the AEAEYAKAK sequence. The novel peptide with double amphiphilic surfaces is different from typical peptides due to special arrangement of the residues. The results of CD, FT-IR, AFM and DLS demonstrate that the peptide with the random coil characteristic was able to form stable nanostructures that were mediated by non-covalent interactions in an aqueous solution. The data further indicated that despite its different structure, the peptide was able to undergo self-assembly similar to a typical peptide. In addition, the use of hydrophobic pyrene as a model allowed the peptide to provide a new type of potential nanomaterial for drug delivery. These efforts collectively open up a new direction in the fabrication of nanomaterials that are more perfect and versatile.

  11. Investigation of Self-assembly Structure and Properties of a Novel Designed Lego-type Peptide with Double Amphiphilic Surfaces

    International Nuclear Information System (INIS)

    Wang, Liang; Zhao, Xiao Jun

    2010-01-01

    A typically designed 'Peptide Lego' has two distinct surfaces: a hydrophilic side that contains the complete charge distribution and a hydrophobic side. In this article, we describe the fabrication of a unique lego-type peptide with the AEAEYAKAK sequence. The novel peptide with double amphiphilic surfaces is different from typical peptides due to special arrangement of the residues. The results of CD, FT-IR, AFM and DLS demonstrate that the peptide with the random coil characteristic was able to form stable nanostructures that were mediated by non-covalent interactions in an aqueous solution. The data further indicated that despite its different structure, the peptide was able to undergo self-assembly similar to a typical peptide. In addition, the use of hydrophobic pyrene as a model allowed the peptide to provide a new type of potential nanomaterial for drug delivery. These efforts collectively open up a new direction in the fabrication of nanomaterials that are more perfect and versatile

  12. Further studies on the structural requirements for mast cell degranulating (MCD) peptide-mediated histamine release.

    Science.gov (United States)

    Buku, A; Price, J A

    2001-12-01

    Mast cell degranulating (MCD) peptide was modified in its two disulfide bridges and in the two arginine residues in order to measure the ability of these analogs to induce histamine release from mast cells in vitro. Analogs prepared were [Ala(3,15)]MCD, [Ala(5,19)]MCD, [Orn(16)]MCD, and [Orn(7,16)]MCD. Their histamine-releasing activity was determined spectrofluorometrically with peritoneal mast cells. The monocyclic analogs in which the cysteine residues were replaced pairwise with alanine residues showed three-to ten-fold diminished histamine-releasing activity respectively, compared with the parent MCD peptide. Substantial increases in activity were observed where arginine residues were replaced by ornithines. The ornithine-mono substituted analog showed an almost six-fold increase and the ornithine-doubly substituted analog three-fold increase in histamine-releasing activity compared with the parent MCD peptide. The structural changes associated with these activities were followed by circular dichroism (CD) spectroscopy. Changes in the shape and ellipticity of the CD spectra reflected a role for the disulfide bonds and the two arginine residues in the overall conformation and biological activity of the molecule.

  13. Impact of graphene-based nanomaterials (GBNMs) on the structural and functional conformations of hepcidin peptide

    Science.gov (United States)

    Singh, Krishna P.; Baweja, Lokesh; Wolkenhauer, Olaf; Rahman, Qamar; Gupta, Shailendra K.

    2018-03-01

    Graphene-based nanomaterials (GBNMs) are widely used in various industrial and biomedical applications. GBNMs of different compositions, size and shapes are being introduced without thorough toxicity evaluation due to the unavailability of regulatory guidelines. Computational toxicity prediction methods are used by regulatory bodies to quickly assess health hazards caused by newer materials. Due to increasing demand of GBNMs in various size and functional groups in industrial and consumer based applications, rapid and reliable computational toxicity assessment methods are urgently needed. In the present work, we investigate the impact of graphene and graphene oxide nanomaterials on the structural conformations of small hepcidin peptide and compare the materials for their structural and conformational changes. Our molecular dynamics simulation studies revealed conformational changes in hepcidin due to its interaction with GBMNs, which results in a loss of its functional properties. Our results indicate that hepcidin peptide undergo severe structural deformations when superimposed on the graphene sheet in comparison to graphene oxide sheet. These observations suggest that graphene is more toxic than a graphene oxide nanosheet of similar area. Overall, this study indicates that computational methods based on structural deformation, using molecular dynamics (MD) simulations, can be used for the early evaluation of toxicity potential of novel nanomaterials.

  14. Functional and structural characterization of recombinant dermcidin-1L, a human antimicrobial peptide

    International Nuclear Information System (INIS)

    Lai Yuping; Peng Yifei; Zuo Yi; Li Jun; Huang Jing; Wang Linfa; Wu Zirong

    2005-01-01

    Antimicrobial peptides from human skin are an important component of the innate immune response and play a key role as a first line of defense against infections. One such peptide is the recently discovered dermcidin-1L. To better understand its mechanism and to further investigate its antimicrobial spectrum, recombinant dermcidin-1L was expressed in Escherichia coli as a fusion protein and purified by affinity chromatography. The fusion protein was cleaved by factor Xa protease to produce recombinant dermcidin-1L. Antimicrobial and hemolytic assays demonstrated that dermcidin-1L displayed microbicidal activity against several opportunistic nosocomial pathogens, but no hemolytic activity against human erythrocytes even at concentrations up to 100 μM. Structural studies performed by circular dichroism spectroscopy indicated that the secondary structure of dermcidin-1L was very flexible, and both α-helix and β-sheet structures might be required for the antimicrobial activity. Our results confirmed previous findings indicating that dermcidin-1L could have promising therapeutic potentials and shed new light on the structure-function relationship of dermcidin-1L

  15. Gas-phase structure and fragmentation pathways of singly protonated peptides with N-terminal arginine.

    Science.gov (United States)

    Bythell, Benjamin J; Csonka, István P; Suhai, Sándor; Barofsky, Douglas F; Paizs, Béla

    2010-11-25

    The gas-phase structures and fragmentation pathways of the singly protonated peptide arginylglycylaspartic acid (RGD) are investigated by means of collision-induced-dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. It is demonstrated that despite the ionizing proton being strongly sequestered at the guanidine group, protonated RGD can easily be fragmented on charge directed fragmentation pathways. This is due to facile mobilization of the C-terminal or aspartic acid COOH protons thereby generating salt-bridge (SB) stabilized structures. These SB intermediates can directly fragment to generate b(2) ions or facilely rearrange to form anhydrides from which both b(2) and b(2)+H(2)O fragments can be formed. The salt-bridge stabilized and anhydride transition structures (TSs) necessary to form b(2) and b(2)+H(2)O are much lower in energy than their traditional charge solvated counterparts. These mechanisms provide compelling evidence of the role of SB and anhydride structures in protonated peptide fragmentation which complements and supports our recent findings for tryptic systems (Bythell, B. J.; Suhai, S.; Somogyi, A.; Paizs, B. J. Am. Chem. Soc. 2009, 131, 14057-14065.). In addition to these findings we also report on the mechanisms for the formation of the b(1) ion, neutral loss (H(2)O, NH(3), guanidine) fragment ions, and the d(3) ion.

  16. Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity.

    Science.gov (United States)

    Mor, A; Chartrel, N; Vaudry, H; Nicolas, P

    1994-10-25

    Pancreatic polypeptide, peptide tyrosine-tyrosine (PYY), and neuropeptide tyrosine (NPY), three members of a family of structurally related peptides, are mainly expressed in the endocrine pancreas, in endocrine cells of the gut, and in the brain, respectively. In the present study, we have isolated a peptide of the pancreatic polypeptide family from the skin of the South American arboreal frog Phyllomedusa bicolor. The primary structure of the peptide was established as Tyr-Pro-Pro-Lys-Pro-Glu-Ser-Pro-Gly-Glu10-Asp-Ala-Ser-Pro-Glu-Glu- Met-Asn- Lys-Tyr20-Leu-Thr-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu30-Val-Thr- Arg-Gln-Arg-Tyr-NH2 . This unusual peptide, named skin peptide tyrosine-tyrosine (SPYY), exhibits 94% similarity with PYY from the frog Rana ridibunda. A synthetic replicate of SPYY inhibits melanotropin release from perifused frog neurointermediate lobes in very much the same way as NPY. These results demonstrate the occurrence of a PYY-like peptide in frog skin. Our data also suggest the existence of a pituitary-skin regulatory loop in amphibians.

  17. How Does Amino Acid Ligand Modulate Au Core Structure and Characteristics in Peptide Coated Au Nanocluster?

    Science.gov (United States)

    Li, Nan; Li, Xu; Zhao, Hongkang; Zhao, Lina

    2018-03-01

    The atomic structures and the corresponding physicochemical properties of peptide coated Au nanoclusters determine their distinctive biological targeting applications. To learn the modulation of amino acid ligand on the atomic structure and electronic characteristics of coated Au core is the fundamental knowledge for peptide coated Au nanocluster design and construction. Based on our recent coated Au nanocluster configuration study (Nanoscale, 2016, 8, 11454), we built the typically simplified Au13(Cys-Au-Cys) system to more clearly learn the basic modulation information of amino acid ligand on Au core by the density functional theory (DFT) calculations. There are two isomers as ligand adjacent bonding (Iso1) and diagonal bonding (Iso2) to Au13 cores. The geometry optimizations indicate the adjacent bonding Iso1 is more stable than Iso2. More important, the Au13 core of Iso1 distorts much more significantly than that of Iso2 by Cys-Au-Cys bonding through the root-mean-square deviation (RMSD) analysis, which modulate their electronic characteristics in different ways. In addition, the frontier molecular orbital results of Au13(Cys-Au-Cys) isomers confirm that the Au cores mainly determine the blue shifts of Au13(Cys-Au-Cys) systems versus the original Au13 core in their UV-visible absorption spectrum studies. The configuration of Au13 core performs deformation under Cys-Au-Cys ligand modulation to reach new stability with distinct atomic structure and electronic properties, which could be the theory basis for peptide coated AuNCs design and construction.

  18. Variational structure of inverse problems in wave propagation and vibration

    Energy Technology Data Exchange (ETDEWEB)

    Berryman, J.G.

    1995-03-01

    Practical algorithms for solving realistic inverse problems may often be viewed as problems in nonlinear programming with the data serving as constraints. Such problems are most easily analyzed when it is possible to segment the solution space into regions that are feasible (satisfying all the known constraints) and infeasible (violating some of the constraints). Then, if the feasible set is convex or at least compact, the solution to the problem will normally lie on the boundary of the feasible set. A nonlinear program may seek the solution by systematically exploring the boundary while satisfying progressively more constraints. Examples of inverse problems in wave propagation (traveltime tomography) and vibration (modal analysis) will be presented to illustrate how the variational structure of these problems may be used to create nonlinear programs using implicit variational constraints.

  19. Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Xiang Chen

    2014-04-01

    Full Text Available Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs and copy number alterations (CNAs. To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%–53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods.

  20. Structure of the superantigen staphylococcal enterotoxin B in complex with TCR and peptide-MHC demonstrates absence of TCR-peptide contacts.

    Science.gov (United States)

    Rödström, Karin E J; Elbing, Karin; Lindkvist-Petersson, Karin

    2014-08-15

    Superantigens are immune-stimulatory toxins produced by Staphylococcus aureus, which are able to interact with host immune receptors to induce a massive release of cytokines, causing toxic shock syndrome and possibly death. In this article, we present the x-ray structure of staphylococcal enterotoxin B (SEB) in complex with its receptors, the TCR and MHC class II, forming a ternary complex. The structure, in combination with functional analyses, clearly shows how SEB adopts a wedge-like position when binding to the β-chain of TCR, allowing for an interaction between the α-chain of TCR and MHC. Furthermore, the binding mode also circumvents contact between TCR and the peptide presented by MHC, which enables SEB to initiate a peptide-independent activation of T cells. Copyright © 2014 by The American Association of Immunologists, Inc.

  1. Probing alpha-helical and beta-sheet structures of peptides at solid/liquid interfaces with SFG.

    Science.gov (United States)

    Chen, Xiaoyun; Wang, Jie; Sniadecki, Jason J; Even, Mark A; Chen, Zhan

    2005-03-29

    We demonstrated that sum frequency generation (SFG) vibrational spectroscopy can distinguish different secondary structures of proteins or peptides adsorbed at solid/liquid interfaces. The SFG spectrum for tachyplesin I at the polystyrene (PS)/solution interface has a fingerprint peak corresponding to the B1/B3 mode of the antiparallel beta-sheet. This peak disappeared upon the addition of dithiothreitol, which can disrupt the beta-sheet structure. The SFG spectrum indicative of the MSI594 alpha-helical structure was observed at the PS/MSI594 solution interface. This research validates SFG as a powerful technique for revealing detailed secondary structures of interfacial proteins and peptides.

  2. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Liu, S.; Kruijtzer, J.A.; Soede, A.C.; Oyen, W.J.G.; Liskamp, R.M.; Corstens, F.H.M.; Boerman, O.C.

    2007-01-01

    INTRODUCTION: Due to the selective expression of the alpha(v)beta3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study,

  3. Fabrication of platinum nanopillars on peptide-based soft structures using a focused ion beam

    International Nuclear Information System (INIS)

    Joshi, K B; Singh, Prabhpreet; Verma, Sandeep

    2009-01-01

    An expedient entry into the construction of bionanocomposites by merging peptide self-assembly, focused ion beam milling, and electron beam-induced deposition is described. Hexapeptides 1 and 2 revealed spherical self-assembled structures which are confirmed by a scanning electron microscope (SEM), atomic force microscope (AFM), focused ion beam/high-resolution scanning electron microscope (FIB-HRSEM), and high-resolution transmission electron microscopy (HRTEM). The microspheres from 1 and 2 are milled with the help of an ion beam to create different shapes. Soft spherical peptide-based structures were also subjected to fabrication under a gallium ion beam, followed by deposition of platinum pillars through a direct write process. It is envisaged that such hybrid bionanocomposites could have applications ranging from Pt-based hydrogenation catalysts to bioelectronics. In addition, such a fabrication process might also be useful to electrically connect two biological systems in order to study an electrical signal or electron transport phenomenon and structural transformations

  4. NMR structure of the Arctic mutation of the Alzheimer's Aβ(1-40) peptide docked to SDS micelles

    Science.gov (United States)

    Usachev, K. S.; Filippov, A. V.; Khairutdinov, B. I.; Antzutkin, O. N.; Klochkov, V. V.

    2014-11-01

    The “Arctic” point mutation of the Alzheimer's amyloid β-peptide is a rare mutation leading to an early onset of Alzheimer's disease. The peptide may interact with neuronal membranes, where it can provide its toxic effects. We used 2D NMR spectroscopy to investigate the conformation of the “Arctic” mutant of Aβ1-40 Alzheimer's amyloid peptide in sodium dodecyl sulfate micelle solutions, which are the type of amphiphilic structures mimicking some properties of biomembranes. The study showed that the Arctic mutant of Aβ1-40 interacts with the surface of SDS micelles mainly through the Leu17-Asn27 310-helical region, while the Ile31-Val40 region is buried in the hydrophobic interior of the micelle. In contrast, wild-type Aβ1-40 interacts with SDS micelles through the Lys16-Asp23 α-helical region and Gly29-Met35. Both the Arctic mutant and the wild-type Aβ1-40 peptides interactions with SDS micelles are hydrophobic in nature. Aβ peptides are thought to be capable of forming pores in biomembranes that can cause changes in neuronal and endothelial cell membrane permeability. It has also been shown that Aβ peptides containing the “Arctic” mutation are more neurotoxic and aggregate more readily than the wild-type Aβ peptides at physiological conditions. Here, we propose that the extension of the helical structure of Leu17-Asn27 and a high aliphaticity (neutrality) of the C-terminal region in the Arctic Aβ peptides are consistent with the idea that formation of ion-permeable pores by Aβ oligomers may be one of prevailing mechanisms of a larger neuronal toxicity of the Arctic Aβ compared to the wild-type Aβ peptides, independent of oxidative damage and lipid peroxidation.

  5. Annual Variation and Global Structures of The DE3 Tide

    International Nuclear Information System (INIS)

    Ze-Yu, Chen; Da-Ren, Lu

    2008-01-01

    The SABER/TIMED temperatures taken in 2002–2006 are used to delineate the tidal signals in the middle and upper atmosphere. Then the Hough mode decomposition is applied with the DE3 tide, and the overall features of the seasonal variations and the complete global structures of the tide are observed. Investigation results show that the tide is most prominent at 110 km with the maximal amplitude of > 9K, and exhibits significant seasonal variation with its maximum amplitude always occurring in July every year. Results from the Hough mode decomposition reveal that the tide is composed primarily of two leading propagating Hough modes, i.e., the (−3,3) and the (−3,4) modes, thus is equatorially trapped. Estimation of the mean amplitude of the Hough modes show that the (−3,3) mode and (−3,4) mode exhibit maxima at 110km and 90 km, respectively. The (−3,3) mode plays a predominant role in shaping the global latitude-height structure of the tide, e.g., the vertical scale of > 50km at the equator, and the annual course. Significant influence of the (−3,4) mode is found below 90km, where the tide exhibits anti-symmetric structure about the equator; meanwhile the tide at northern tropical latitudes exhibits smaller vertical wavelength of about 30 km. (geophysics, astronomy, and astrophysics)

  6. Structure and further fragmentation of significant [a3 + Na - H]+ ions from sodium-cationized peptides.

    Science.gov (United States)

    Wang, Huixin; Wang, Bing; Wei, Zhonglin; Zhang, Hao; Guo, Xinhua

    2015-01-01

    A good understanding of gas-phase fragmentation chemistry of peptides is important for accurate protein identification. Additional product ions obtained by sodiated peptides can provide useful sequence information supplementary to protonated peptides and improve protein identification. In this work, we first demonstrate that the sodiated a3 ions are abundant in the tandem mass spectra of sodium-cationized peptides although observations of a3 ions have rarely been reported in protonated peptides. Quantum chemical calculations combined with tandem mass spectrometry are used to investigate this phenomenon by using a model tetrapeptide GGAG. Our results reveal that the most stable [a3 + Na - H](+) ion is present as a bidentate linear structure in which the sodium cation coordinates to the two backbone carbonyl oxygen atoms. Due to structural inflexibility, further fragmentation of the [a3 + Na - H](+) ion needs to overcome several relatively high energetic barriers to form [b2 + Na - H](+) ion with a diketopiperazine structure. As a result, low abundance of [b2 + Na - H](+) ion is detected at relatively high collision energy. In addition, our computational data also indicate that the common oxazolone pathway to generate [b2 + Na - H](+) from the [a3 + Na - H](+) ion is unlikely. The present work provides a mechanistic insight into how a sodium ion affects the fragmentation behaviors of peptides. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Molecular structure and diversity of PBAN/Pyrokinin family peptides in ants

    Directory of Open Access Journals (Sweden)

    Man-Yeon eChoi

    2012-02-01

    Full Text Available Neuropeptides are the largest group of insect hormones. They are produced in the central and peripheral nervous systems and affect insect development, reproduction, feeding and behavior. A variety of neuropeptide families have been identified in insects. One of these families is the PBAN/pyrokinin family defined by a common FXPRLamide or similar amino acid fragment at the C-terminal end. These peptides, found in all insects studied thus far, have been conserved throughout evolution. The most well studied physiological function is regulation of moth sex pheromone biosynthesis through the Pheromone Biosynthesis Activating Neurohormone (PBAN, although several developmental functions have also been reported. Over the past years we have extended knowledge of the PBAN/pyrokinin family of peptides to ants, focusing mainly on the fire ant, Solenopsis invicta. The fire ant is one of the most studied social insects and over the last 60 years a great deal has been learned about many aspects of this ant, including the behaviors and chemistry of pheromone communication. However, virtually nothing is known about the regulation of these pheromone systems. Recently, we demonstrated the presence of PBAN/pyrokinin immunoreactive neurons in the fire ant, and identified and characterized PBAN and additional neuropeptides. We have mapped the fire ant PBAN gene structure and determined the tissue expression level in the central nervous system of the ant. We review here our research to date on the molecular structure and diversity of ant PBAN/pyrokinin peptides in preparation for determining the function of the neuropeptides in ants and other social insects.

  8. Structural and pharmacological characteristics of chimeric peptides derived from peptide E and beta-endorphin reveal the crucial role of the C-terminal YGGFL and YKKGE motifs in their analgesic properties.

    Science.gov (United States)

    Condamine, Eric; Courchay, Karine; Rego, Jean-Claude Do; Leprince, Jérôme; Mayer, Catherine; Davoust, Daniel; Costentin, Jean; Vaudry, Hubert

    2010-05-01

    Peptide E (a 25-amino acid peptide derived from proenkephalin A) and beta-endorphin (a 31-amino acid peptide derived from proopiomelanocortin) bind with high affinity to opioid receptors and share structural similarities but induce analgesic effects of very different intensity. Indeed, whereas they possess the same N-terminus Met-enkephalin message sequence linked to a helix by a flexible spacer and a C-terminal part in random coil conformation, in contrast with peptide E, beta-endorphin produces a profound analgesia. To determine the key structural elements explaining this very divergent opioid activity, we have compared the structural and pharmacological characteristics of several chimeric peptides derived from peptide E and beta-endorphin. Structures were obtained under the same experimental conditions using circular dichroism, computational estimation of helical content and/or nuclear magnetic resonance spectroscopy (NMR) and NMR-restrained molecular modeling. The hot-plate and writhing tests were used in mice to evaluate the antinociceptive effects of the peptides. Our results indicate that neither the length nor the physicochemical profile of the spacer plays a fundamental role in analgesia. On the other hand, while the functional importance of the helix cannot be excluded, the last 5 residues in the C-terminal part seem to be crucial for the expression or absence of the analgesic activity of these peptides. These data raise the question of the true function of peptides E in opioidergic systems. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  9. FEA of the Variations in Sound Insulation in Nominally Identical Prefabricated Lightweight Timber Panel Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Andersen, Lars

    2013-01-01

    The measurements of sound propagation in buildings usually show a variation between nominally identical constructed structures. These variations can be due to variations in structural properties, measurement uncertainties or workmanship related factors. Better knowledge about the source...... for these variations can lead to lowered production costs. The present paper presents a numerical analysis of the variations in sound propagation of norminally identical prefabricated lightweight timber panel structues. By using the commercial FEA software ABAQUS, a parameter study is carried out regarding variation...

  10. Crystal structure of importin-{alpha} complexed with a classic nuclear localization sequence obtained by oriented peptide library screening

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, A.A.S.; Fontes, M.R.M. [UNESP, Universidade Estadual Paulista, Botucatu, SP (Brazil); Yang, S.N.Y. [University of Melbourne, Melbourne (Australia); Harris, J.M. [Queensland University of Technology, Brisbane (Australia); Jans, D.A. [Monash University, Clayton (Australia); Kobe, B. [University of Queensland, Brisbane, QU (Australia)

    2012-07-01

    Full text: Importin-{alpha} (Imp{alpha}) plays a role in the classical nuclear import pathway, binding to cargo proteins with activities in the nucleus. Different Imp{alpha} paralogs responsible for specific cargos can be found in a single organism. The cargos contain nuclear localization sequences (NLSs), which are characterized by one or two clusters of basic amino acids (monopartite and bipartite NLSs, respectively). In this work we present the crystal structure of Imp{alpha} from M. musculus (residues 70-529, lacking the auto inhibitory domain) bound to a NLS peptide (pepTM). The peptide corresponds to the optimal sequence obtained by an oriented peptide library experiment designed to probe the specificity of the major NLS binding site. The peptide library used five degenerate positions and identified the sequence KKKRR as the optimal sequence for binding to this site for mouse Imp{alpha} (70-529). The protein was obtained using an E. coli expression system and purified by affinity chromatography followed by an ion exchange chromatography. A single crystal of Imp{alpha} -pepTM complex was grown by the hanging drop method. The data were collected using the Synchrotron Radiation Source LNLS, Brazil and processed to 2.3. Molecular replacement techniques were used to determine the crystal structure. Electron density corresponding to the peptide was present in both major and minor binding sites The peptide is bound to Imp{alpha} similar as the simian virus 40 (SV40) large tumour (T)-antigen NLS. Binding assays confirmed that the peptide bound to Imp{alpha} with low nM affinities. This is the first time that structural information has been linked to an oriented peptide library screening approach for importin-{alpha}; the results will contribute to understanding of the sequence determinants of classical NLSs, and may help identify as yet unidentified classical NLSs in novel proteins. (author)

  11. Using Gas-Phase Guest-Host Chemistry to Probe the Structures of b Ions of Peptides

    Science.gov (United States)

    Somogyi, Árpád; Harrison, Alex G.; Paizs, Béla

    2012-12-01

    Middle-sized b n ( n ≥ 5) fragments of protonated peptides undergo selective complex formation with ammonia under experimental conditions typically used to probe hydrogen-deuterium exchange in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Other usual peptide fragments like y, a, a*, etc., and small b n ( n ≤ 4) fragments do not form stable ammonia adducts. We propose that complex formation of b n ions with ammonia is characteristic to macrocyclic isomers of these fragments. Experiments on a protonated cyclic peptide and N-terminal acetylated peptides fully support this hypothesis; the protonated cyclic peptide does form ammonia adducts while linear b n ions of acetylated peptides do not undergo complexation. Density functional theory (DFT) calculations on the proton-bound dimers of all-Ala b 4 , b 5 , and b 7 ions and ammonia indicate that the ionizing proton initially located on the peptide fragment transfers to ammonia upon adduct formation. The ammonium ion is then solvated by N+-H…O H-bonds; this stabilization is much stronger for macrocyclic b n isomers due to the stable cage-like structure formed and entropy effects. The present study demonstrates that gas-phase guest-host chemistry can be used to selectively probe structural features (i.e., macrocyclic or linear) of fragments of protonated peptides. Stable ammonia adducts of b 9 , b 9 -A, and b 9 -2A of A8YA, and b 13 of A20YVFL are observed indicating that even these large b-type ions form macrocyclic structures.

  12. Rotational stellar structures based on the Lagrangian variational principle

    International Nuclear Information System (INIS)

    Yasutake, Nobutoshi; Fujisawa, Kotaro; Yamada, Shoichi

    2017-01-01

    A new method for multi-dimensional stellar structures is proposed in this study. As for stellar evolution calculations, the Heney method is the defacto standard now, but basically assumed to be spherical symmetric. It is one of the difficulties for deformed stellar-evolution calculations to trace the potentially complex movements of each fluid element. On the other hand, our new method is very suitable to follow such movements, since it is based on the Lagrange coordinate. This scheme is also based on the variational principle, which is adopted to the studies for the pasta structures inside of neutron stars. Our scheme could be a major break through for evolution calculations of any types of deformed stars: proto-planets, proto-stars, and proto-neutron stars, etc. (paper)

  13. Rotational stellar structures based on the Lagrangian variational principle

    Science.gov (United States)

    Yasutake, Nobutoshi; Fujisawa, Kotaro; Yamada, Shoichi

    2017-06-01

    A new method for multi-dimensional stellar structures is proposed in this study. As for stellar evolution calculations, the Heney method is the defacto standard now, but basically assumed to be spherical symmetric. It is one of the difficulties for deformed stellar-evolution calculations to trace the potentially complex movements of each fluid element. On the other hand, our new method is very suitable to follow such movements, since it is based on the Lagrange coordinate. This scheme is also based on the variational principle, which is adopted to the studies for the pasta structures inside of neutron stars. Our scheme could be a major break through for evolution calculations of any types of deformed stars: proto-planets, proto-stars, and proto-neutron stars, etc.

  14. Solution structures of the linear leaderless bacteriocins enterocin 7A and 7B resemble carnocyclin A, a circular antimicrobial peptide.

    Science.gov (United States)

    Lohans, Christopher T; Towle, Kaitlyn M; Miskolzie, Mark; McKay, Ryan T; van Belkum, Marco J; McMullen, Lynn M; Vederas, John C

    2013-06-11

    Leaderless bacteriocins are a class of ribosomally synthesized antimicrobial peptides that are produced by certain Gram-positive bacteria without an N-terminal leader section. These bacteriocins are of great interest due to their potent inhibition of many Gram-positive organisms, including food-borne pathogens such as Listeria and Clostridium spp. We now report the NMR solution structures of enterocins 7A and 7B, leaderless bacteriocins recently isolated from Enterococcus faecalis 710C. These are the first three-dimensional structures to be reported for bacteriocins of this class. Unlike most other linear Gram-positive bacteriocins, enterocins 7A and 7B are highly structured in aqueous conditions. Both peptides are primarily α-helical, adopting a similar overall fold. The structures can be divided into three separate α-helical regions: the N- and C-termini are both α-helical, separated by a central kinked α-helix. The overall structures bear an unexpected resemblance to carnocyclin A, a 60-residue peptide that is cyclized via an amide bond between the C- and N-termini and has a saposin fold. Because of synergism observed for other two-peptide leaderless bacteriocins, it was of interest to probe possible binding interactions between enterocins 7A and 7B. However, despite synergistic activity observed between these peptides, no significant binding interaction was observed based on NMR and isothermal calorimetry.

  15. Two-dimensional sum-frequency generation (2D SFG) reveals structure and dynamics of a surface-bound peptide

    Science.gov (United States)

    Laaser, Jennifer E.; Skoff, David R.; Ho, Jia-Jung; Joo, Yongho; Serrano, Arnaldo L.; Steinkruger, Jay D.; Gopalan, Padma; Gellman, Samuel H.; Zanni, Martin T.

    2014-01-01

    Surface-bound polypeptides and proteins are increasingly used to functionalize inorganic interfaces such as electrodes, but their structural characterization is exceedingly difficult with standard technologies. In this paper, we report the first two-dimensional sum-frequency generation (2D SFG) spectra of a peptide monolayer, which is collected by adding a mid-IR pulse shaper to a standard femtosecond SFG spectrometer. On a gold surface, standard FTIR spectroscopy is inconclusive about the peptide structure because of solvation-induced frequency shifts, but the 2D lineshapes, anharmonic shifts, and lifetimes obtained from 2D SFG reveal that the peptide is largely α-helical and upright. Random coil residues are also observed, which do not themselves appear in SFG spectra due to their isotropic structural distribution, but which still absorb infrared light and so can be detected by cross-peaks in 2D SFG spectra. We discuss these results in the context of peptide design. Because of the similar way in which the spectra are collected, these 2D SFG spectra can be directly compared to 2D IR spectra, thereby enabling structural interpretations of surface-bound peptides and biomolecules based on the well-studied structure/2D IR spectra relationships established from soluble proteins. PMID:24372101

  16. Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

    Science.gov (United States)

    Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

    2018-06-01

    The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Recognition and Binding of a Helix-Loop-Helix Peptide to Carbonic Anhydrase Occurs via Partly Folded Intermediate Structures

    Science.gov (United States)

    Lignell, Martin; Becker, Hans-Christian

    2010-01-01

    Abstract We have studied the association of a helix-loop-helix peptide scaffold carrying a benzenesulfonamide ligand to carbonic anhydrase using steady-state and time-resolved fluorescence spectroscopy. The helix-loop-helix peptide, developed for biosensing applications, is labeled with the fluorescent probe dansyl, which serves as a polarity-sensitive reporter of the binding event. Using maximum entropy analysis of the fluorescence lifetime of dansyl at 1:1 stoichiometry reveals three characteristic fluorescence lifetime groups, interpreted as differently interacting peptide/protein structures. We characterize these peptide/protein complexes as mostly bound but unfolded, bound and partly folded, and strongly bound and folded. Furthermore, analysis of the fluorescence anisotropy decay resulted in three different dansyl rotational correlation times, namely 0.18, 1.2, and 23 ns. Using the amplitudes of these times, we can correlate the lifetime groups with the corresponding fluorescence anisotropy component. The 23-ns rotational correlation time, which appears with the same amplitude as a 17-ns fluorescence lifetime, shows that the dansyl fluorophore follows the rotational diffusion of carbonic anhydrase when it is a part of the folded peptide/protein complex. A partly folded and partly hydrated interfacial structure is manifested in an 8-ns dansyl fluorescence lifetime and a 1.2-ns rotational correlation time. This structure, we believe, is similar to a molten-globule-like interfacial structure, which allows segmental movement and has a higher degree of solvent exposure of dansyl. Indirect excitation of dansyl on the helix-loop-helix peptide through Förster energy transfer from one or several tryptophans in the carbonic anhydrase shows that the helix-loop-helix scaffold binds to a tryptophan-rich domain of the carbonic anhydrase. We conclude that binding of the peptide to carbonic anhydrase involves a transition from a disordered to an ordered structure of the

  18. Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode

    International Nuclear Information System (INIS)

    Ye, Q.; Li, X.; Wong, A.; Wei, Q.; Jia, Z.

    2006-01-01

    Calcineurin is a calmodulin-binding protein in brain and the only serine/threonine protein phosphatase under the control of Ca 2+ /calmodulin (CaM), which plays a critical role in coupling Ca 2+ signals to cellular responses. CaM up-regulates the phosphatase activity of calcineurin by binding to the CaM-binding domain (CBD) of calcineurin subunit A. Here, we report crystal structural studies of CaM bound to a CBD peptide. The chimeric protein containing CaM and the CBD peptide forms an intimate homodimer, in which CaM displays a native-like extended conformation and the CBD peptide shows -helical structure. Unexpectedly, the N-terminal lobe from one CaM and the C-terminal lobe from the second molecule form a combined binding site to trap the peptide. Thus, the dimer provides two binding sites, each of which is reminiscent of the fully collapsed conformation of CaM commonly observed in complex with, for example, the myosin light chain kinase (MLCK) peptide. The interaction between the peptide and CaM is highly specific and similar to MLCK

  19. Interaction of the chaperone calreticulin with proteins and peptides of different structural classes

    DEFF Research Database (Denmark)

    Duus, K; Sandhu, N; Jørgensen, C S

    2009-01-01

    The interaction of calreticulin with native and denatured forms and polypeptides in proteolytic digests of proteins representing structural classes of all-alpha-helix (hemoglobin, serum albumin), all-beta-sheet (IgG) and alpha-helix + beta-sheets (lysozyme, ovalbumin) was investigated. The binding...... of calreticulin to denatured proteins was found to depend on conformation and structural class of the protein. No interaction was observed with the native proteins, whereas binding was seen for the denatured proteins, the order of interaction being lysozyme = IgG > ovalbumin >> hemoglobin = serum albumin....... Moreover, the interaction between calreticulin and the heat-denatured proteins depended on the temperature and time used for denaturation and the degree of proteolytic fragmentation. Calreticulin bound well to peptides in proteolytic digests from protease K or chymotrypsin treatment of lysozyme, Ig...

  20. Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide

    Science.gov (United States)

    Wang, Yukun; Chen, Charles H.; Hu, Dan; Ulmschneider, Martin B.; Ulmschneider, Jakob P.

    2016-11-01

    Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures--formed by a single sequence--may be a key feature in preventing bacterial resistance and could explain why sequence-function relationships in AMPs remain elusive.

  1. Novel Concepts of MS-Cleavable Cross-linkers for Improved Peptide Structure Analysis

    Science.gov (United States)

    Hage, Christoph; Falvo, Francesco; Schäfer, Mathias; Sinz, Andrea

    2017-10-01

    The chemical cross-linking/mass spectrometry (MS) approach is gaining increasing importance as an alternative method for studying protein conformation and for deciphering protein interaction networks. This study is part of our ongoing efforts to develop innovative cross-linking principles for a facile and efficient assignment of cross-linked products. We evaluate two homobifunctional, amine-reactive, and MS-cleavable cross-linkers regarding their potential for automated analysis of cross-linked products. We introduce the bromine phenylurea (BrPU) linker that possesses a unique structure yielding a distinctive fragmentation pattern on collisional activation. Moreover, BrPU delivers the characteristic bromine isotope pattern and mass defect for all cross-linker-decorated fragments. We compare the fragmentation behavior of the BrPU linker with that of our previously described MS-cleavable TEMPO-Bz linker (which consists of a 2,2,6,6-tetramethylpiperidine-1-oxy moiety connected to a benzyl group) that was developed to perform free-radical-initiated peptide sequencing. Comparative collisional activation experiments (collision-induced dissociation and higher-energy collision-induced dissociation) with both cross-linkers were conducted in negative electrospray ionization mode with an Orbitrap Fusion mass spectrometer using five model peptides. As hypothesized in a previous study, the presence of a cross-linked N-terminal aspartic acid residue seems to be the prerequisite for the loss of an intact peptide from the cross-linked products. As the BrPU linker combines a characteristic mass shift with an isotope signature, it presents a more favorable combination for automated assignment of cross-linked products compared with the TEMPO-Bz linker. [Figure not available: see fulltext.

  2. Structural system identification based on variational mode decomposition

    Science.gov (United States)

    Bagheri, Abdollah; Ozbulut, Osman E.; Harris, Devin K.

    2018-03-01

    In this paper, a new structural identification method is proposed to identify the modal properties of engineering structures based on dynamic response decomposition using the variational mode decomposition (VMD). The VMD approach is a decomposition algorithm that has been developed as a means to overcome some of the drawbacks and limitations of the empirical mode decomposition method. The VMD-based modal identification algorithm decomposes the acceleration signal into a series of distinct modal responses and their respective center frequencies, such that when combined their cumulative modal responses reproduce the original acceleration response. The decaying amplitude of the extracted modal responses is then used to identify the modal damping ratios using a linear fitting function on modal response data. Finally, after extracting modal responses from available sensors, the mode shape vector for each of the decomposed modes in the system is identified from all obtained modal response data. To demonstrate the efficiency of the algorithm, a series of numerical, laboratory, and field case studies were evaluated. The laboratory case study utilized the vibration response of a three-story shear frame, whereas the field study leveraged the ambient vibration response of a pedestrian bridge to characterize the modal properties of the structure. The modal properties of the shear frame were computed using analytical approach for a comparison with the experimental modal frequencies. Results from these case studies demonstrated that the proposed method is efficient and accurate in identifying modal data of the structures.

  3. Detection of trans-cis flips and peptide-plane flips in protein structures

    NARCIS (Netherlands)

    Touw, W.G.; Joosten, R.P.; Vriend, G.

    2015-01-01

    A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans-cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans-cis flips and many thousands of hitherto unknown

  4. Structural determination of nanomolar quantities of neuroactive peptides by nuclear magnetic resonance

    Science.gov (United States)

    Matei, Elena

    The specificity of the conotoxin is one of the attributes that make them a valuable diagnostic tool in the characterization of neuronal mechanisms, or therapeutic agents in medicine. It appears that Nature has provided us with a pharmaceutical tool in the form of Conus peptides. Further studies will only enhance our understanding, and use, of these molecules in medicine and science. The study of three-dimensional structure in relation to the function of cone snail peptides is an area of increasing interest. The venom of a single cone snail can contain as many as 300 different chemical components. Individual cone snail venom components, or conopeptides, can have powerful neurological effects. For many interesting species, not enough venom collected from the natural origin is available for experimental investigations. After a laborious separation procedure, only nanomole quantities of these native conopeptides are able to be obtained. Therefore, several experimental applications, such as NMR spectroscopy, are difficult to carry out using traditional methods. The research was focused on using nanoNMR spectroscopy as an alternative method to the conventional NMR spectroscopy method in order to analyze small quantities of novel peptides with unknown three-dimensional conformational arrangement. The experimental results obtained using the HR-MAS NMR technique, in addition to the use of a 3mm gHCN (with 1.7mm inserts) NMR probes, proved the capability of conformational analysis of different types of natural products at sample levels down to nanomole range. Understanding the interaction between agonist or antagonist ligands and their target receptors, at a molecular level, offer promise for the development of pharmacological therapeutics for the central nervous system. Conopeptides are of great interest as ligands in neuroscience and are valuable leads in drug design, based on their specificity and potency for therapeutically relevant receptors and ion channels. For

  5. Polarization switching and patterning in self-assembled peptide tubular structures

    Science.gov (United States)

    Bdikin, Igor; Bystrov, Vladimir; Delgadillo, Ivonne; Gracio, José; Kopyl, Svitlana; Wojtas, Maciej; Mishina, Elena; Sigov, Alexander; Kholkin, Andrei L.

    2012-04-01

    Self-assembled peptide nanotubes are unique nanoscale objects that have great potential for a multitude of applications, including biosensors, nanotemplates, tissue engineering, biosurfactants, etc. The discovery of strong piezoactivity and polar properties in aromatic dipeptides [A. Kholkin, N. Amdursky, I. Bdikin, E. Gazit, and G. Rosenman, ACS Nano 4, 610 (2010)] opened up a new perspective for their use as biocompatible nanoactuators, nanomotors, and molecular machines. Another, as yet unexplored functional property is the ability to switch polarization and create artificial polarization patterns useful in various electronic and optical applications. In this work, we demonstrate that diphenylalanine peptide nanotubes are indeed electrically switchable if annealed at a temperature of about 150 °C. The new orthorhombic antipolar structure that appears after annealing allows for the existence of a radial polarization component, which is directly probed by piezoresponse force microscopy (PFM) measurements. Observation of the relatively stable polarization patterns and hysteresis loops via PFM testifies to the local reorientation of molecular dipoles in the radial direction. The experimental results are complemented with rigorous molecular calculations and create a solid background of electric-field induced deformation of aromatic rings and corresponding polarization switching in this emergent material.

  6. Insights into structural variations and genome rearrangements in prokaryotic genomes.

    Science.gov (United States)

    Periwal, Vinita; Scaria, Vinod

    2015-01-01

    Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Sensing site-specific structural characteristics and chirality using vibrational circular dichroism of isotope labeled peptides.

    Science.gov (United States)

    Keiderling, Timothy A

    2017-12-01

    Isotope labeling has a long history in chemistry as a tool for probing structure, offering enhanced sensitivity, or enabling site selection with a wide range of spectroscopic tools. Chirality sensitive methods such as electronic circular dichroism are global structural tools and have intrinsically low resolution. Consequently, they are generally insensitive to modifications to enhance site selectivity. The use of isotope labeling to modify vibrational spectra with unique resolvable frequency shifts can provide useful site-specific sensitivity, and these methods have been recently more widely expanded in biopolymer studies. While the spectral shifts resulting from changes in isotopic mass can provide resolution of modes from specific parts of the molecule and can allow detection of local change in structure with perturbation, these shifts alone do not directly indicate structure or chirality. With vibrational circular dichroism (VCD), the shifted bands and their resultant sign patterns can be used to indicate local conformations in labeled biopolymers, particularly if multiple labels are used and if their coupling is theoretically modeled. This mini-review discusses selected examples of the use of labeling specific amides in peptides to develop local structural insight with VCD spectra. © 2017 Wiley Periodicals, Inc.

  8. Ligand-induced changes in the structure and dynamics of Escherichia coli peptide deformylase.

    Science.gov (United States)

    Amero, Carlos D; Byerly, Douglas W; McElroy, Craig A; Simmons, Amber; Foster, Mark P

    2009-08-18

    Peptide deformylase (PDF) is an enzyme that is responsible for removing the formyl group from nascently synthesized polypeptides in bacteria, attracting much attention as a potential target for novel antibacterial agents. Efforts to develop potent inhibitors of the enzyme have progressed on the basis of classical medicinal chemistry, combinatorial chemistry, and structural approaches, yet the validity of PDF as an antibacterial target hangs, in part, on the ability of inhibitors to selectively target this enzyme in favor of structurally related metallohydrolases. We have used (15)N NMR spectroscopy and isothermal titration calorimetry to investigate the high-affinity interaction of EcPDF with actinonin, a naturally occurring potent EcPDF inhibitor. Backbone amide chemical shifts, residual dipolar couplings, hydrogen-deuterium exchange, and (15)N relaxation reveal structural and dynamic effects of ligand binding in the immediate vicinity of the ligand-binding site as well as at remote sites. A comparison of the crystal structures of free and actinonin-bound EcPDF with the solution data suggests that most of the consequences of the ligand binding to the protein are lost or obscured during crystallization. The results of these studies improve our understanding of the thermodynamic global minimum and have important implications for structure-based drug design.

  9. Structure, Content, and Bioactivity of Food-Derived Peptides in the Body.

    Science.gov (United States)

    Sato, Kenji

    2018-03-28

    Orally administered peptides are assumed to be degraded into amino acids in the body. However, our recent studies revealed some food-derived prolyl and pyroglutamyl peptides with 2-3 amino acid residues in the blood of humans and animals, while most of the peptides in the endoproteinase digest of food protein are degraded by exopeptidase. Some food-derived dipeptides in the body display in vitro and in vivo biological activities. These facts indicate that the biological activities of food-derived peptides in the body rather than those in food are crucial to understanding the mechanism of the beneficial effects of orally administered peptides.

  10. Structure, synthesis, and activity of dermaseptin b, a novel vertebrate defensive peptide from frog skin: relationship with adenoregulin.

    Science.gov (United States)

    Mor, A; Amiche, M; Nicolas, P

    1994-05-31

    A novel antimicrobial peptide, designated dermaseptin b, was isolated from the skin of the arboreal frog Phyllomedusa bicolor. This 27-residue peptide amide is basic, containing 3 lysine residues that punctuate an alternating hydrophobic and hydrophilic sequence. In helix-inducing solvent, dermaseptin b adopts an amphipathic alpha-helical conformation that most closely resembles class L amphipathic helixes, with all lysine residues on the polar face of the helix. The peptide exhibits growth inhibition activity in vitro against a broad spectrum of pathogenic microorganisms including yeast and bacteria as well as various filamentous fungi that are responsible for severe opportunistic infections accompanying acquired immunodeficiency syndrome and the use of immunosuppressive agents. Maximized pairwise sequence alignment of dermaseptin b and dermaseptin s, a 34-residue antimicrobial peptide previously isolated from Phyllomedusa sauvagii, reveals 81% amino acid identity. No other significant similarity was found between dermaseptin b and any prokaryotic or eukaryotic protein, but similarity was found with adenoregulin (38% amino acid postional identity), a 33-residue peptide that enhances binding of agonists to the A1 adenosine receptor. The synthetic replicates of dermaseptin b and adenoregulin displayed similar but nonidentical spectra of antimicrobial activity, and both peptides were devoid of lytic effect on mammalian cells. Accordingly, the observation that adenoregulin enhances binding of agonists to the adenosine receptor may in fact be a consequence of its ability to alter the structure of biological membranes and to produce signal transduction via interactions with the lipid bilayer, bypassing cell surface receptor interactions.

  11. Detection of trans–cis flips and peptide-plane flips in protein structures

    International Nuclear Information System (INIS)

    Touw, Wouter G.; Joosten, Robbie P.; Vriend, Gert

    2015-01-01

    A method is presented to detect peptide bonds that need either a trans–cis flip or a peptide-plane flip. A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans–cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. A few examples are highlighted for which a correction of the peptide-plane geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely available and the method is available from a web server, a web-service interface and through WHAT-CHECK

  12. Detection of trans–cis flips and peptide-plane flips in protein structures

    Energy Technology Data Exchange (ETDEWEB)

    Touw, Wouter G., E-mail: wouter.touw@radboudumc.nl [Radboud University Medical Center, Geert Grooteplein-Zuid 26-28, 6525 GA Nijmegen (Netherlands); Joosten, Robbie P. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Vriend, Gert, E-mail: wouter.touw@radboudumc.nl [Radboud University Medical Center, Geert Grooteplein-Zuid 26-28, 6525 GA Nijmegen (Netherlands)

    2015-07-28

    A method is presented to detect peptide bonds that need either a trans–cis flip or a peptide-plane flip. A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans–cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. A few examples are highlighted for which a correction of the peptide-plane geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely available and the method is available from a web server, a web-service interface and through WHAT-CHECK.

  13. Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach

    International Nuclear Information System (INIS)

    Economou, Nicoleta J.; Zentner, Isaac J.; Lazo, Edwin; Jakoncic, Jean; Stojanoff, Vivian; Weeks, Stephen D.; Grasty, Kimberly C.; Cocklin, Simon; Loll, Patrick J.

    2013-01-01

    Using a carrier-protein strategy, the structure of teicoplanin bound to its bacterial cell-wall target has been determined. The structure reveals the molecular determinants of target recognition, flexibility in the antibiotic backbone and intrinsic radiation sensitivity of teicoplanin. Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by binding and sequestering a cell-wall precursor: a d-alanine-containing peptide. A carrier-protein strategy was used to crystallize the complex of teicoplanin and its target peptide by fusing the cell-wall peptide to either MBP or ubiquitin via native chemical ligation and subsequently crystallizing the protein–peptide–antibiotic complex. The 2.05 Å resolution MBP–peptide–teicoplanin structure shows that teicoplanin recognizes its ligand through a combination of five hydrogen bonds and multiple van der Waals interactions. Comparison of this teicoplanin structure with that of unliganded teicoplanin reveals a flexibility in the antibiotic peptide backbone that has significant implications for ligand recognition. Diffraction experiments revealed an X-ray-induced dechlorination of the sixth amino acid of the antibiotic; it is shown that teicoplanin is significantly more radiation-sensitive than other similar antibiotics and that ligand binding increases radiosensitivity. Insights derived from this new teicoplanin structure may contribute to the development of next-generation antibacterials designed to overcome bacterial resistance

  14. Structural Characterization by NMR of a Double Phosphorylated Chimeric Peptide Vaccine for Treatment of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Stefan Berger

    2013-04-01

    Full Text Available Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer’s disease (AD and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau229-237[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B241-255 originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible.

  15. Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

    International Nuclear Information System (INIS)

    Ivancic, Monika; Daly, Roger J.; Lyons, Barbara A.

    2003-01-01

    The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central β-sheet capped at each end by an α-helix. The presence of a four residue insertion in the region between β-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a β-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed

  16. Structural analysis of peptides capable of binding to more than one Ia antigen

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Colon, S

    1989-01-01

    The Ia binding regions were analyzed for three unrelated peptide Ag (sperm whale myoglobin 106-118, influenza hemagglutinin 130-142, and lambda repressor protein 12-26) for which binding to more than one Ia molecule has previously been demonstrated. By determining the binding profile of three...... separate series of truncated synthetic peptides, it was found that in all three cases the different Ia reactivities mapped to largely overlapping regions of the peptides; although, for two of the peptides, the regions involved in binding the different Ia specificities were distinct. Moreover, subtle...... differences were found to dramatically influence some, but not other, Ia reactivities. Using a large panel of synthetic peptides it was found that a significant correlation exists between the capacity of peptides to interact with different alleles of the same molecule (i.e., IAd and IAk), but no correlation...

  17. Simulation of Major Histocompatibility Complex (MHC Structure and Peptide Loading into an MHC Binding Pocket with Teachers’Hands

    Directory of Open Access Journals (Sweden)

    Mojtaba Sankian

    2013-10-01

    Full Text Available Molecular understanding of three-dimensional (3D peptide: MHC models require both basic knowledge of computational modeling and skilled visual perception, which are not possessed by all students. The present model aims to simulate MHC molecular structure with the hands and make a profound impression on the students.

  18. Structure-activity-based design of a synthetic malaria peptide eliciting sporozoite inhibitory antibodies in a virosomal formulation.

    NARCIS (Netherlands)

    Okitsu, S.L.; Kienzl, U.; Moehle, K.; Silvie, O.; Peduzzi, E.; Mueller, M.S.; Sauerwein, R.W.; Matile, H.; Zurbriggen, R.; Mazier, D.; Robinson, J.A.; Pluschke, G.

    2007-01-01

    The circumsporozoite protein (CSP) of Plasmodium falciparum is a leading candidate antigen for inclusion in a malaria subunit vaccine. We describe here the design of a conformationally constrained synthetic peptide, designated UK-39, which has structural and antigenic similarity to the NPNA-repeat

  19. NMR solution structure of poliovirus uridylyated peptide linked to the genome (VPgpU)

    Science.gov (United States)

    Schein, Catherine H.; Oezguen, Numan; van der Heden van Noort, Gerbrand J.; Filippov, Dmitri V.; Paul, Aniko; Kumar, Eric; Braun, Werner

    2010-01-01

    Picornaviruses have a 22–24 amino acid peptide, VPg, bound covalently at the 5’ end of their RNA, that is essential for replication. VPgs are uridylylated at a conserved Tyrosine to form VPgpU, the primer of RNA synthesis by the viral polymerase. This first complete structure for any uridylylated VPg, of poliovirus type 1 (PV1)-VPgpU, shows that conserved amino acids in VPg stabilize the bound UMP, with the uridine atoms involved in base pairing and chain elongation projected outward. Comparing this structure to PV1-VPg and partial structures of VPg/VPgpU from other picornaviruses suggests that enteroviral polymerases require a more stable VPg structure than does the distantly related aphthovirus, foot and mouth disease virus (FMDV). The glutamine residue at the C-terminus of PV1-VPgpU lies in back of the uridine base and may stabilize its position during chain elongation and/or contribute to base specificity. Under in vivo-like conditions with the authentic cre(2C) hairpin RNA and Mg++, 5-methylUTP cannot compete with UTP for VPg uridylyation in an in vitro uridylyation assay, but both nucleotides are equally incorporated by PV1-polymerase with Mn++ and a poly-A RNA template. This indicates the 5 position is recognized under in vivo conditions. The compact VPgpU structure docks within the active site cavity of the PV-polymerase, close to the position seen for the fragment of FMDV-VPgpU with its polymerase. This structure could aid in design of novel enterovirus inhibitors, and stabilization upon uridylylation may also be pertinent for post-translational uridylylation reactions that underlie other biological processes. PMID:20441784

  20. Hemin and bile pigments are the secondary structure regulators of intrinsically disordered antimicrobial peptides.

    Science.gov (United States)

    Zsila, Ferenc; Juhász, Tünde; Bősze, Szilvia; Horváti, Kata; Beke-Somfai, Tamás

    2018-02-01

    The interaction of protoporphyrin compounds of human origin with the major bee venom component melittin (26 a.a., Z +6) and its hybrid derivative (CM15, 15 a.a., Z +6) were studied by a combination of various spectroscopic methods. Throughout a two-state, concentration-dependent process, hemin and its metabolites (biliverdin, bilirubin, bilirubin ditaurate) increase the parallel β-sheet content of the natively unfolded melittin, suggesting the oligomerization of the peptide chains. In contrast, α-helix promoting effect was observed with the also disordered but more cationic CM15. According to fluorescence quenching experiments, the sole Trp residue of melittin is the key player during the binding, in the vicinity of which the first pigment molecule is accommodated presumably making indole-porphyrin π-π stacking interaction. As circular dichroism titration data suggest, cooperative association of additional ligands subsequently occurs, resulting in multimeric complexes with an apparent dissociation constant ranged from 20 to 65 μM. Spectroscopic measurements conducted with the bilirubin catabolite urobilin and stercobilin refer to the requirement of intact dipyrrinone moieties for inducing secondary structure transformations. The binding topography of porphyrin rings on a model parallel β-sheet motif was evaluated by absorption spectroscopy and computational modeling showing a slipped-cofacial binding mode responsible for the red shift and hypochromism of the Soret band. Our results may aid to recognize porphyrin-responsive binding motifs of biologically relevant, intrinsically disordered peptides and proteins, where transient conformations play a vital role in their functions. © 2017 Wiley Periodicals, Inc.

  1. Statistically significant dependence of the Xaa-Pro peptide bond conformation on secondary structure and amino acid sequence

    Directory of Open Access Journals (Sweden)

    Leitner Dietmar

    2005-04-01

    Full Text Available Abstract Background A reliable prediction of the Xaa-Pro peptide bond conformation would be a useful tool for many protein structure calculation methods. We have analyzed the Protein Data Bank and show that the combined use of sequential and structural information has a predictive value for the assessment of the cis versus trans peptide bond conformation of Xaa-Pro within proteins. For the analysis of the data sets different statistical methods such as the calculation of the Chou-Fasman parameters and occurrence matrices were used. Furthermore we analyzed the relationship between the relative solvent accessibility and the relative occurrence of prolines in the cis and in the trans conformation. Results One of the main results of the statistical investigations is the ranking of the secondary structure and sequence information with respect to the prediction of the Xaa-Pro peptide bond conformation. We observed a significant impact of secondary structure information on the occurrence of the Xaa-Pro peptide bond conformation, while the sequence information of amino acids neighboring proline is of little predictive value for the conformation of this bond. Conclusion In this work, we present an extensive analysis of the occurrence of the cis and trans proline conformation in proteins. Based on the data set, we derived patterns and rules for a possible prediction of the proline conformation. Upon adoption of the Chou-Fasman parameters, we are able to derive statistically relevant correlations between the secondary structure of amino acid fragments and the Xaa-Pro peptide bond conformation.

  2. Common and divergent structural features of a series of corticotropin releasing factor-related peptides.

    Science.gov (United States)

    Grace, Christy Rani R; Perrin, Marilyn H; Cantle, Jeffrey P; Vale, Wylie W; Rivier, Jean E; Riek, Roland

    2007-12-26

    Members of the corticoliberin family include the corticotropin releasing factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure activity relationship studies led to several potent and long-acting analogues with selective binding to either one of the receptors. NMR structures of six ligands of this family (the antagonists astressin B and astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show differences in binding affinities, receptor-selectivity, and NMR structure. Overall, their backbones are alpha-helical, with a small kink or a turn around residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are of amphipathic nature, whereas the N-terminal helices vary in their amphipathicity. The C-terminal helices thereby assume a conformation very similar to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1 On the basis of an analysis of the observed 3D structures and relative potencies of [Ala]-substituted analogues, it is proposed that both helices could play a crucial role in receptor binding and selectivity. In conclusion, the C-terminal helices may interact along their hydrophobic faces with the ECD1, whereas the entire N-terminal helical surface may be involved in receptor activation. On the basis of the common and divergent features observed in the 3D structures of these ligands, multiple binding models are proposed that may explain their plurality of actions.

  3. Isolation, structure, synthesis, and activity of a new member of the calcitonin gene-related peptide family from frog skin and molecular cloning of its precursor.

    Science.gov (United States)

    Seon, A A; Pierre, T N; Redeker, V; Lacombe, C; Delfour, A; Nicolas, P; Amiche, M

    2000-02-25

    Calcitonin gene-related peptide has been extracted from the skin exudate of a single living specimen of the frog Phyllomedusa bicolor and purified to homogeneity by a two-step protocol. A total volume of 250 microl of exudate yielded 380 microg of purified peptide. Mass spectrometric analysis and gas phase sequencing of the purified peptide as well as chemical synthesis and cDNA analysis were consistent with the structure SCDTSTCATQRLADFLSRSGGIGSPDFVPTDVSANSF amide and the presence of a disulfide bridge linking Cys(2) and Cys(7). The skin peptide, named skin calcitonin gene-related peptide, differs significantly from all other members of the calcitonin gene-related peptide family of peptides at nine positions but binds with high affinity to calcitonin gene-related peptide receptors in the rat brain and acts as an agonist in the rat vas deferens bioassay with potencies equal to those of human CGRP. Reverse transcriptase-polymerase chain reaction coupled with cDNA cloning and sequencing demonstrated that skin calcitonin gene-related peptide isolated in the skin is identical to that present in the frog's central and enteric nervous systems. These data, which indicate for the first time the existence of calcitonin gene-related peptide in the frog skin, add further support to the brain-skin-gut triangle hypothesis as a useful tool in the identification and/or isolation of mammalian peptides that are present in the brain and other tissues in only minute quantities.

  4. [Natriuretic peptides. History of discovery, chemical structure, mechanism of action and the removal routes. Basis of diagnostic and therapeutic use].

    Science.gov (United States)

    Stryjewski, Piotr J; Nessler, Bohdan; Cubera, Katarzyna; Nessler, Jadwiga

    2013-01-01

    Natriuretic peptides (NP) are the group of proteins synthesized and secreted by the mammalian heart. All the NP are synthesized from prohormones and have 17-amino acid cyclic structures containing two cysteine residues linked by internal disulphide bond. They are characterized by a wide range of actions, mainly through their membrane receptors. The NP regulate the water and electrolyte balance, blood pressure through their diuretic, natriuretic, and relaxating the vascular smooth muscles effects. They also affect the endocrine system and the nervous system. The neurohormonal regulation of blood circulation results are mainly based on antagonism with renin--angiotensin--aldosterone system. The NP representatives are: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), urodilatine and (DNP) Dendroaspis natriuretic peptide, not found in the human body. According to the guidelines of the European Society of Cardiology determination of NT-proBNP level have found a use in the diagnosis of acute and chronic heart failure, risk stratification in acute coronary syndromes and pulmonary embolism. There are reports found in the literature, that demonstrate the usefulness of NT-proBNP determination in valvular, atrial fibrillation, and syncopes. Recombinant human ANP--Carperitid and BNP--Nesiritid, have already found a use in the adjunctive therapy of dyspnea in acute heart failure.

  5. Three-residue turns in alpha/beta-peptides and their application in the design of tertiary structures.

    Science.gov (United States)

    Sharma, Gangavaram V M; Nagendar, Pendem; Ramakrishna, Kallaganti V S; Chandramouli, Nagula; Choudhary, Madavi; Kunwar, Ajit C

    2008-06-02

    A new three-residue turn was serendipitously discovered in alpha/beta hybrid peptides derived from alternating C-linked carbo-beta-amino acids (beta-Caa) and L-Ala residues. The three-residue beta-alpha-beta turn at the C termini, nucleated by a helix at the N termini, resulted in helix-turn (HT) supersecondary structures in these peptides. The turn in the HT motif is stabilized by two H bonds-CO(i-2)-NH(i), with a seven-membered pseudoring (gamma turn) in the backward direction, and NH(i-2)-CO(i), with a 13-membered pseudoring in the forward direction (i being the last residue)--at the C termini. The study was extended to generalize the new three-residue turn (beta-alpha-beta) by using different alpha- and beta-amino acids. Furthermore, the HT motifs were efficiently converted, by an extension with helical oligomers at the C termini, into peptides with novel helix-turn-helix (HTH) tertiary structures. However, this resulted in the destabilization of the beta-alpha-beta turn with the concomitant nucleation of another three-residue turn, alpha-beta-beta, which is stabilized by 11- and 15-membered bifurcated H bonds. Extensive NMR spectroscopic studies were carried out to delineate the secondary and tertiary structures in these peptides, which are further supported by molecular dynamics (MD) investigations.

  6. Structure-activity study of macropin, a novel antimicrobial peptide from the venom of solitary bee Macropis fulvipes (Hymenoptera: Melittidae).

    Science.gov (United States)

    Monincová, Lenka; Veverka, Václav; Slaninová, Jiřina; Buděšínský, Miloš; Fučík, Vladimír; Bednárová, Lucie; Straka, Jakub; Ceřovský, Václav

    2014-06-01

    A novel antimicrobial peptide, designated macropin (MAC-1) with sequence Gly-Phe-Gly-Met-Ala-Leu-Lys-Leu-Leu-Lys-Lys-Val-Leu-NH2 , was isolated from the venom of the solitary bee Macropis fulvipes. MAC-1 exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria, antifungal activity, and moderate hemolytic activity against human red blood cells. A series of macropin analogs were prepared to further evaluate the effect of structural alterations on antimicrobial and hemolytic activities and stability in human serum. The antimicrobial activities of several analogs against pathogenic Pseudomonas aeruginosa were significantly increased while their toxicity against human red blood cells was decreased. The activity enhancement is related to the introduction of either l- or d-lysine in selected positions. Furthermore, all-d analog and analogs with d-amino acid residues introduced at the N-terminal part of the peptide chain exhibited better serum stability than did natural macropin. Data obtained by CD spectroscopy suggest a propensity of the peptide to adopt an amphipathic α-helical secondary structure in the presence of trifluoroethanol or membrane-mimicking sodium dodecyl sulfate. In addition, the study elucidates the structure-activity relationship for the effect of d-amino acid substitutions in MAC-1 using NMR spectroscopy. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

  7. Use of synthetic analogues in confirmation of structure of the peptide antibiotics Maltacines

    Science.gov (United States)

    Hagelin, Gunnar; Indrevoll, Bård; Hoeg-Jensen, Thomas

    2007-12-01

    Maltacines comprise a family of cyclic peptide lactone antibiotics produced by a strain of Bacillus subtilis. The previously proposed amino acid sequences of the linear ring-opened molecules show similarity to the lipopeptide antibiotic Fengycin IX that is also produced by a strain of B. subtilisE There were some discrepancies in the Maltacin data that could not be explained. To address this and gain more information into the structure of the linear ring-opened Maltacines, the two members D1c, E1b and Fengycin IX acid were synthesised and their MS2, MS3 and MS4 spectra compared. The similarity of the product ion spectra of Maltacin and Fengycin IX acid revealed that proline occupies an internal position in Maltacin. This finding led to revision of the interpretation of the amino acid sequences of the Maltacines. The proposed new structures of the Maltacines shows that the cyclic part of the molecules is the same as in Fengycin IX acid and Fengycin XII acid, but they have unique N-terminal sequences not found in Fengycins, and thus represent novel lipopeptide antibiotics.

  8. Protein and Peptide Gas-phase Structure Investigation Using Collision Cross Section Measurements and Hydrogen Deuterium Exchange

    Science.gov (United States)

    Khakinejad, Mahdiar

    Protein and peptide gas-phase structure analysis provides the opportunity to study these species outside of their explicit environment where the interaction network with surrounding molecules makes the analysis difficult [1]. Although gas-phase structure analysis offers a unique opportunity to study the intrinsic behavior of these biomolecules [2-4], proteins and peptides exhibit very low vapor pressures [2]. Peptide and protein ions can be rendered in the gas-phase using electrospray ionization (ESI) [5]. There is a growing body of literature that shows proteins and peptides can maintain solution structures during the process of ESI and these structures can persist for a few hundred milliseconds [6-9]. Techniques for monitoring gas-phase protein and peptide ion structures are categorized as physical probes and chemical probes. Collision cross section (CCS) measurement, being a physical probe, is a powerful method to investigate gas-phase structure size [3, 7, 10-15]; however, CCS values alone do not establish a one to one relation with structure(i.e., the CCS value is an orientationally averaged value [15-18]. Here we propose the utility of gas-phase hydrogen deuterium exchange (HDX) as a second criterion of structure elucidation. The proposed approach incudes extensive MD simulations to sample biomolecular ion conformation space with the production of numerous, random in-silico structures. Subsequently a CCS can be calculated for these structures and theoretical CCS values are compared with experimental values to produce a pool of candidate structures. Utilizing a chemical reaction model based on the gas-phase HDX mechanism, the HDX kinetics behavior of these candidate structures are predicted and compared to experimental results to nominate the best in-silico structures which match (chemically and physically) with experimental observations. For the predictive approach to succeed, an extensive technique and method development is essential. To combine CCS

  9. Structural study of a novel antimicrobial peptide isolated from the venom of bee Anthophora plumipes

    Czech Academy of Sciences Publication Activity Database

    Čujová, Sabína; Veverka, Václav; Buděšínský, Miloš; Bednárová, Lucie; Čeřovský, Václav

    2014-01-01

    Roč. 20, Suppl S1 (2014), S263-S264 ISSN 1075-2617. [European Peptide Symposium /33./. 31.08.2014-05.09.2014, Sofia] Institutional support: RVO:61388963 Keywords : antimicrobial peptides * membranes * CD-spectroscopy * NMR spectroscopy Subject RIV: CC - Organic Chemistry

  10. Structural basis for the enhanced activity of cyclic antimicrobial peptides : The case of BPC194

    NARCIS (Netherlands)

    Mika, Jacek T.; Moiset, Gemma; Cirac, Anna D.; Feliu, Lidia; Bardaji, Eduard; Planas, Marta; Sengupta, Durba; Marrink, Siewert J.; Poolman, Bert

    We report the molecular basis for the differences in activity of cyclic and linear antimicrobial peptides. We iteratively performed atomistic molecular dynamics simulations and biophysical measurements to probe the interaction of a cyclic antimicrobial peptide and its inactive linear analogue with

  11. Influence of hydrophobic Teflon particles on the structure of amyloid beta-peptide

    NARCIS (Netherlands)

    Giacomelli, C.E.; Norde, W.

    2003-01-01

    The amyloid beta-protein (Abeta) constitutes the major peptide component of the amyloid plaque deposits of Alzheimer's disease in humans. The Abeta changes from a nonpathogenic to a pathogenic conformation resulting in self-aggregation and deposition of the peptide. It has been established that

  12. Structure and Dynamics Studies of Cytolytic Peptides in Lipid Bilayers using NMR Spectroscopy

    DEFF Research Database (Denmark)

    Hansen, Sara Krogh

    2015-01-01

    different and cytolytic peptides were investigated in this work. The peptides were SPF-5506-A4 from Trichoderma sp, Conolysin-Mt1 from Conus mustelinus, and Alamethicin from Trichoderma viride. The studies employed solution and solid-state NMR spectroscopy in combination with different biophysical methods...

  13. Effects of the KIF2C neck peptide on microtubules: lateral disintegration of microtubules and β-structure formation.

    Science.gov (United States)

    Shimizu, Youské; Shimizu, Takashi; Nara, Masayuki; Kikumoto, Mahito; Kojima, Hiroaki; Morii, Hisayuki

    2013-04-01

    Members of the kinesin-13 sub-family, including KIF2C, depolymerize microtubules. The positive charge-rich 'neck' region extending from the N-terminus of the catalytic head is considered to be important in the depolymerization activity. Chemically synthesized peptides, covering the basic region (A182-E200), induced a sigmoidal increase in the turbidity of a microtubule suspension. The increase was suppressed by salt addition or by reduction of basicity by amino acid substitutions. Electron microscopic observations revealed ring structures surrounding the microtubules at high peptide concentrations. Using the peptide A182-D218, we also detected free thin straight filaments, probably protofilaments disintegrated from microtubules. Therefore, the neck region, even without the catalytic head domain, may induce lateral disintegration of microtubules. With microtubules lacking anion-rich C-termini as a result of subtilisin treatment, addition of the peptide induced only a moderate increase in turbidity, and rings and protofilaments were rarely detected, while aggregations, also thought to be caused by lateral disintegration, were often observed in electron micrographs. Thus, the C-termini are not crucial for the action of the peptides in lateral disintegration but contribute to structural stabilization of the protofilaments. Previous structural studies indicated that the neck region of KIF2C is flexible, but our IR analysis suggests that the cation-rich region (K190-A204) forms β-structure in the presence of microtubules, which may be of significance with regard to the action of the neck region. Therefore, the neck region of KIF2C is sufficient to cause disintegration of microtubules into protofilaments, and this may contribute to the ability of KIF2C to cause depolymerization of microtubules. © 2013 The Authors Journal compilation © 2013 FEBS.

  14. Gene structure, transcripts and calciotropic effects of the PTH family of peptides in Xenopus and chicken

    Directory of Open Access Journals (Sweden)

    Power Deborah M

    2010-12-01

    Full Text Available Abstract Background Parathyroid hormone (PTH and PTH-related peptide (PTHrP belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34 and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken. Results The PTH-L gene is present throughout the vertebrates with the exception of placental mammals. Gene structure of PTH and PTH-L seems to be conserved in vertebrates while PTHrP gene structure is divergent and has acquired new exons and alternative promoters. Splice variants of PTHrP and PTH-L are common in Xenopus and chicken and transcripts of the former have a widespread tissue distribution, although PTH-L is more restricted. PTH is widely expressed in fish tissue but from Xenopus to mammals becomes largely restricted to the parathyroid gland. The N-terminal (1-34 region of PTH, PTHrP and PTH-L in Xenopus and chicken share high sequence conservation and the capacity to modify calcium fluxes across epithelia suggesting a conserved role in calcium metabolism possibly via similar receptors. Conclusions The parathyroid hormone family contains 3 principal members, PTH, PTHrP and the recently identified PTH-L. In teleosts there are 5 genes which encode PTHrP (2, PTH (2 and PTH-L and in tetrapods there are 3 genes (PTHrP, PTH and PTH-L, the exception is placental mammals which

  15. Exploring biological effects of MoS{sub 2} nanosheets on native structures of α-helical peptides

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Zonglin; Li, Weifeng, E-mail: wfli@suda.edu.cn, E-mail: ruhong@us.ibm.com [School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123 (China); Hong, Linbi [Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Zhou, Ruhong, E-mail: wfli@suda.edu.cn, E-mail: ruhong@us.ibm.com [School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123 (China); Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Department of Chemistry, Columbia University, New York, New York 10027 (United States)

    2016-05-07

    Recent reports of mono- and few-layer molybdenum disulfide (MoS{sub 2}), a representative transition metal dichacogenide (TMD), as antibacterial and anticancer agents have shed light on their potential in biomedical applications. To better facilitate these promising applications, one needs to understand the biological effects of these TMDs as well, such as their potential adverse effects on protein structure and function. Here, we sought to understand the interaction of MoS{sub 2} nanosheets with peptides using molecular dynamics simulations and a simple model polyalanine with various lengths (PA{sub n}, n = 10, 20, 30, and 40; mainly α − helices). Our results demonstrated that MoS{sub 2} monolayer has an exceptional capability to bind all peptides in a fast and strong manner. The strong attraction from the MoS{sub 2} nanosheet is more than enough to compensate the energy needed to unfold the peptide, regardless of the length, which induces drastic disruptions to the intra-peptide hydrogen bonds and subsequent secondary structures of α − helices. This universal phenomenon may point to the potential nanotoxicity of MoS{sub 2} when used in biological systems. Moreover, these results aligned well with previous findings on the potential cytotoxicity of TMD nanomaterials.

  16. Exploring biological effects of MoS2 nanosheets on native structures of α-helical peptides

    International Nuclear Information System (INIS)

    Gu, Zonglin; Li, Weifeng; Hong, Linbi; Zhou, Ruhong

    2016-01-01

    Recent reports of mono- and few-layer molybdenum disulfide (MoS 2 ), a representative transition metal dichacogenide (TMD), as antibacterial and anticancer agents have shed light on their potential in biomedical applications. To better facilitate these promising applications, one needs to understand the biological effects of these TMDs as well, such as their potential adverse effects on protein structure and function. Here, we sought to understand the interaction of MoS 2 nanosheets with peptides using molecular dynamics simulations and a simple model polyalanine with various lengths (PA n , n = 10, 20, 30, and 40; mainly α − helices). Our results demonstrated that MoS 2 monolayer has an exceptional capability to bind all peptides in a fast and strong manner. The strong attraction from the MoS 2 nanosheet is more than enough to compensate the energy needed to unfold the peptide, regardless of the length, which induces drastic disruptions to the intra-peptide hydrogen bonds and subsequent secondary structures of α − helices. This universal phenomenon may point to the potential nanotoxicity of MoS 2 when used in biological systems. Moreover, these results aligned well with previous findings on the potential cytotoxicity of TMD nanomaterials.

  17. Protein Phosphorylation and Mineral Binding Affect the Secondary Structure of the Leucine-Rich Amelogenin Peptide

    Directory of Open Access Journals (Sweden)

    Hajime Yamazaki

    2017-06-01

    Full Text Available Previously, we have shown that serine-16 phosphorylation in native full-length porcine amelogenin (P173 and the Leucine-Rich Amelogenin Peptide (LRAP(+P, an alternative amelogenin splice product, affects protein assembly and mineralization in vitro. Notably, P173 and LRAP(+P stabilize amorphous calcium phosphate (ACP and inhibit hydroxyapatite (HA formation, while non-phosphorylated counterparts (rP172, LRAP(−P guide the growth of ordered bundles of HA crystals. Based on these findings, we hypothesize that the phosphorylation of full-length amelogenin and LRAP induces conformational changes that critically affect its capacity to interact with forming calcium phosphate mineral phases. To test this hypothesis, we have utilized Fourier transform infrared spectroscopy (FTIR to determine the secondary structure of LRAP(−P and LRAP(+P in the absence/presence of calcium and selected mineral phases relevant to amelogenesis; i.e., hydroxyapatite (HA: an enamel crystal prototype and (ACP: an enamel crystal precursor phase. Aqueous solutions of LRAP(−P or LRAP(+P were prepared with or without 7.5 mM of CaCl2 at pH 7.4. FTIR spectra of each solution were obtained using attenuated total reflectance, and amide-I peaks were analyzed to provide secondary structure information. Secondary structures of LRAP(+P and LRAP(−P were similarly assessed following incubation with suspensions of HA and pyrophosphate-stabilized ACP. Amide I spectra of LRAP(−P and LRAP(+P were found to be distinct from each other in all cases. Spectra analyses showed that LRAP(−P is comprised mostly of random coil and β-sheet, while LRAP(+P exhibits more β-sheet and α-helix with little random coil. With added Ca, the random coil content increased in LRAP(−P, while LRAP(+P exhibited a decrease in α-helix components. Incubation of LRAP(−P with HA or ACP resulted in comparable increases in β-sheet structure. Notably, however, LRAP(+P secondary structure was more affected by

  18. Cation-pi interactions stabilize the structure of the antimicrobial peptide indolicidin near membranes: molecular dynamics simulations

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N

    2007-01-01

    We implemented molecular dynamics simulations of the 13-residue antimicrobial peptide indolicidin (ILPWKWPWWPWRR-NH2) in dodecylphosphocholine (DPC) and sodium dodecyl sulfate (SDS) micelles. In DPC, a persistent cation-pi interaction between TRP11 and ARG13 defined the structure of the peptide...... near the interface. A transient cation-pi interaction was also observed between TRP4 and the choline group on DPC lipids. We also implemented simulation of a mutant of indolicidin in the DPC micelle where TRP11 was replaced by ALA11. As a result of the mutation, the boat-shaped conformation is lost...... and the structure becomes significantly less defined. On the basis of this evidence, we argue that cation-pi interactions determine the experimentally measured, well-defined boat-shaped structure of indolicidin. In SDS, the lack of such interactions and the electrostatic binding of the terminal arginine residues...

  19. Solution structure of the first SH3 domain of human vinexin and its interaction with vinculin peptides

    International Nuclear Information System (INIS)

    Zhang, Jiahai; Li, Xiang; Yao, Bo; Shen, Weiqun; Sun, Hongbin; Xu, Chao; Wu, Jihui; Shi, Yunyu

    2007-01-01

    Solution structure of the first Src homology (SH) 3 domain of human vinexin (V S H3 1 ) was determined using nuclear magnetic resonance (NMR) method and revealed that it was a canonical SH3 domain, which has a typical β-β-β-β-α-β fold. Using chemical shift perturbation and surface plasmon resonance experiments, we studied the binding properties of the SH3 domain with two different peptides from vinculin hinge regions: P856 and P868. The observations illustrated slightly different affinities of the two peptides binding to V S H3 1 . The interaction between P868 and V S H3 1 belonged to intermediate exchange with a modest binding affinity, while the interaction between P856 and V S H3 1 had a low binding affinity. The structure and ligand-binding interface of V S H3 1 provide a structural basis for the further functional study of this important molecule

  20. Effects of truncation of the peptide chain on the secondary structure and bioactivities of palmitoylated anoplin.

    Science.gov (United States)

    Salas, Remmer L; Garcia, Jan Kathryne D L; Miranda, Ana Carmela R; Rivera, Windell L; Nellas, Ricky B; Sabido, Portia Mahal G

    2018-06-01

    Anoplin (GLLKRIKTLL-NH 2 ) is of current interest due to its short sequence and specificity towards bacteria. Recent studies on anoplin have shown that truncation and acylation compromises its antimicrobial activity and specificity, respectively. In this study, truncated analogues (pal-ano-9 to pal-ano-5) of palmitoylated anoplin (pal-anoplin) were synthesized to determine the effects of C-truncation on its bioactivities. Moreover, secondary structure of each analogue using circular dichroism (CD) spectroscopy was determined to correlate with bioactivities. Interestingly, pal-anoplin, pal-ano-9 and pal-ano-6 were helical in water, unlike anoplin. In contrast, pal-ano-8, pal-ano-7 and pal-ano-5, with polar amino acid residues at the C-terminus, were random coil in water. Nevertheless, all the peptides folded into helical structures in 30% trifluoroethanol/water (TFE/H 2 O) except for the shortest analogue pal-ano-5. Hydrophobicity played a significant role in the enhancement of activity against bacteria E. coli and S. aureus as all lipopeptides including the random coil pal-ano-5 were more active than the parent anoplin. Meanwhile, the greatest improvement in activity against the fungus C. albicans was observed for pal-anoplin analogues (pal-ano-9 and pal-ano-6) that were helical in water. Although, hydrophobicity is a major factor in the secondary structure and antimicrobial activity, it appears that the nature of amino acids at the C-terminus also influence folding of lipopeptides in water and its antifungal activity. Moreover, the hemolytic activity of the analogues was found to correlate with hydrophobicity, except for the least hemolytic, pal-ano-5. Since most of the analogues are more potent and shorter than anoplin, they are promising drug candidates for further development. Copyright © 2018. Published by Elsevier Inc.

  1. High-resolution NMR structure of the antimicrobial peptide protegrin-2 in the presence of DPC micelles

    Energy Technology Data Exchange (ETDEWEB)

    Usachev, K. S., E-mail: k.usachev@kpfu.ru; Efimov, S. V.; Kolosova, O. A.; Filippov, A. V.; Klochkov, V. V. [Kazan Federal University (Russian Federation)

    2015-04-15

    PG-1 adopts a dimeric structure in dodecylphosphocholine (DPC) micelles, and a channel is formed by the association of several dimers but the molecular mechanisms of the membrane damage by non-α-helical peptides are still unknown. The formation of the PG-1 dimer is important for pore formation in the lipid bilayer, since the dimer can be regarded as the primary unit for assembly into the ordered aggregates. It was supposed that only 12 residues (RGGRL-CYCRR-RFCVC-V) are needed to endow protegrin molecules with strong antibacterial activity and that at least four additional residues are needed to add potent antifungal properties. Thus, the 16-residue protegrin (PG-2) represents the minimal structure needed for broad-spectrum antimicrobial activity encompassing bacteria and fungi. As the peptide conformation and peptide-to-membrane binding properties are very sensitive to single amino acid substitutions, the solution structure of PG-2 in solution and in a membrane mimicking environment are crucial. In order to find evidence if the oligomerization state of PG-1 in a lipid environment will be the same or not for another protegrins, we investigate in the present work the PG-2 NMR solution structure in the presence of perdeuterated DPC micelles. The NMR study reported in the present work indicates that PG-2 form a well-defined structure (PDB: 2MUH) composed of a two-stranded antiparallel β-sheet when it binds to DPC micelles.

  2. Spatial Structure and Temporal Variation of Fish Communities in the Upper Mississippi River System

    National Research Council Canada - National Science Library

    Chick, John H; Ickes, Brian S; Pegg, Mark A; Barko, Valerie A; Hrabik, Robert A; Herzog, David P

    2005-01-01

    Variation in community composition (presence/absence data) and structure (relative abundance) of Upper Mississippi River fishes was assessed using data from the Long Term Resource Monitoring Program...

  3. Landscape and variation of RNA secondary structure across the human transcriptome.

    OpenAIRE

    Wan, Y; Qu, K; Zhang, QC; Flynn, RA; Manor, O; Ouyang, Z; Zhang, J; Spitale, RC; Snyder, MP; Segal, E; Chang, HY

    2014-01-01

    In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comp...

  4. Discrete variational methods and their application to electronic structures

    International Nuclear Information System (INIS)

    Ellis, D.E.

    1987-01-01

    Some general concepts concerning Discrete Variational methods are developed and applied to problems of determination of eletronic spectra, charge densities and bonding of free molecules, surface-chemisorbed species and bulk solids. (M.W.O.) [pt

  5. Structure-Based Drug Design of Small Molecule Peptide Deformylase Inhibitors to Treat Cancer

    Directory of Open Access Journals (Sweden)

    Jian Gao

    2016-03-01

    Full Text Available Human peptide deformylase (HsPDF is an important target for anticancer drug discovery. In view of the limited HsPDF, inhibitors were reported, and high-throughput virtual screening (HTVS studies based on HsPDF for developing new PDF inhibitors remain to be reported. We reported here on diverse small molecule inhibitors with excellent anticancer activities designed based on HTVS and molecular docking studies using the crystal structure of HsPDF. The compound M7594_0037 exhibited potent anticancer activities against HeLa, A549 and MCF-7 cell lines with IC50s of 35.26, 29.63 and 24.63 μM, respectively. Molecular docking studies suggested that M7594_0037 and its three derivatives could interact with HsPDF by several conserved hydrogen bonds. Moreover, the pharmacokinetic and toxicity properties of M7594_0037 and its derivatives were predicted using the OSIRIS property explorer. Thus, M7594_0037 and its derivatives might represent a promising scaffold for the further development of novel anticancer drugs.

  6. Electronic structure, dielectric response, and surface charge distribution of RGD (1FUV) peptide.

    Science.gov (United States)

    Adhikari, Puja; Wen, Amy M; French, Roger H; Parsegian, V Adrian; Steinmetz, Nicole F; Podgornik, Rudolf; Ching, Wai-Yim

    2014-07-08

    Long and short range molecular interactions govern molecular recognition and self-assembly of biological macromolecules. Microscopic parameters in the theories of these molecular interactions are either phenomenological or need to be calculated within a microscopic theory. We report a unified methodology for the ab initio quantum mechanical (QM) calculation that yields all the microscopic parameters, namely the partial charges as well as the frequency-dependent dielectric response function, that can then be taken as input for macroscopic theories of electrostatic, polar, and van der Waals-London dispersion intermolecular forces. We apply this methodology to obtain the electronic structure of the cyclic tripeptide RGD-4C (1FUV). This ab initio unified methodology yields the relevant parameters entering the long range interactions of biological macromolecules, providing accurate data for the partial charge distribution and the frequency-dependent dielectric response function of this peptide. These microscopic parameters determine the range and strength of the intricate intermolecular interactions between potential docking sites of the RGD-4C ligand and its integrin receptor.

  7. Structure-activity studies of vasoactive intestinal peptide (VIP): cyclic disulfide analogs.

    Science.gov (United States)

    Bolin, D R; Cottrell, J; Garippa, R; O'Neill, N; Simko, B; O'Donnell, M

    1993-02-01

    Analogs of vasoactive intestinal peptide with cysteine residues incorporated at selected sites within the sequence were prepared by solid phase methods, oxidized to the corresponding cyclic disulfides and purified to homogeneity by preparative HPLC. The cyclic compounds were assayed as smooth muscle relaxants on isolated guinea pig trachea, as bronchodilators in vivo in guinea pigs, and for binding to VIP receptors in guinea pig lung membranes. Of the analogs prepared at the N-terminus, one compound, Ac-[D-Cys6,D-Cys11,Lys12,Nle17,Val26,Th r28]-VIP, was found to be a full agonist with slightly more than one tenth the potency of native VIP. Most other cyclic analogs in the N-terminal region were found to be inactive. A second analog, Ac-[Lys12,Cys17,Val26,Cys28]-VIP, was also found to be a full agonist with potency about one third that of native VIP. Furthermore, this compound was active as a bronchodilator in vivo in guinea pig, but with somewhat diminished potency as compared to native VIP. Strikingly, this cyclic compound was found to have significantly longer duration of action (> 40 min) when compared to an analogous acyclic compound (5 min). The conformational restrictions imposed by formation of the cyclic ring structures may have stabilized the molecule to degradation, thus enhancing the effective duration of action. Analysis of this series of cyclic analogs has also yielded information about the requirements for the receptor-active conformation of VIP.

  8. Ligand and Structure-Based Approaches for the Identification of Peptide Deformylase Inhibitors as Antibacterial Drugs.

    Science.gov (United States)

    Gao, Jian; Liang, Li; Zhu, Yasheng; Qiu, Shengzhi; Wang, Tao; Zhang, Ling

    2016-07-15

    Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins, which makes it an important antibacterial drug target. Given the importance of PDF inhibitors like actinonin in antibacterial drug discovery, several reported potent PDF inhibitors were used to develop pharmacophore models using the Galahad module of Sybyl 7.1 software. Generated pharmacophore models were composed of two donor atom centers, four acceptor atom centers and two hydrophobic groups. Model-1 was screened against the Zinc database and several compounds were retrieved as hits. Compounds with Qfit values of more than 60 were employed to perform a molecular docking study with the receptor Escherichia coli PDF, then compounds with docking score values of more than 6 were used to predict the in silico pharmacokinetic and toxicity risk via OSIRIS property explorer. Two known PDF inhibitors were also used to perform a molecular docking study with E. coli PDF as reference molecules. The results of the molecular docking study were validated by reproducing the crystal structure of actinonin. Molecular docking and in silico pharmacokinetic and toxicity prediction studies suggested that ZINC08740166 has a relatively high docking score of 7.44 and a drug score of 0.78.

  9. Structure of a SARS coronavirus-derived peptide bound to the human major histocompatibility complex class I molecule HLA-B*1501

    DEFF Research Database (Denmark)

    Røder, Gustav; Kristensen, Ole; Kastrup, Jette S

    2008-01-01

    , the crystal structure of HLA-B*1501 in complex with a SARS coronavirus-derived nonapeptide (VQQESSFVM) has been determined at high resolution (1.87 A). The peptide is deeply anchored in the B and F pockets, but with the Glu4 residue pointing away from the floor in the peptide-binding groove, making...

  10. Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide

    International Nuclear Information System (INIS)

    Dijkgraaf, Ingrid; Liu, Shuang; Kruijtzer, John A.W.; Soede, Annemieke C.; Oyen, Wim J.G.; Liskamp, Rob M.J.; Corstens, Frans H.M.; Boerman, Otto C.

    2007-01-01

    Introduction: Due to the selective expression of the α v β 3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study, we systematically investigated the effects of linker modification between two cyclic RGD sequences and DOTA (1,4,7,10-tetraazadodecane-N,N',N ' ,N'''-tetraacetic acid) on the in vitro and in vivo characteristics of the tracer. Methods: A dimeric RGD peptide was synthesized and conjugated either directly with DOTA or via different linkers: PEG 4 (polyethylene glycol), glutamic acid or lysine. The RGD peptides were radiolabeled with 111 In, and their in vitro and in vivo α v β 3 -binding characteristics were determined. Results: LogP values varied between -2.82±0.06 and -3.95±0.33. The IC 50 values for DOTA-E-[c(RGDfK)] 2 , DOTA-PEG 4 -E-[c(RGDfK)] 2 , DOTA-E-E-[c(RGDfK)] 2 and DOTA-K-E-[c(RGDfK)] 2 were comparable. Two hours after injection, the tumor uptakes of the 111 In-labeled compounds were not significantly different. The kidney accumulation of [ 111 In]-DOTA-K-E-[c(RGDfK)] 2 [4.05±0.20% of the injected dose per gram (ID/g)] was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (2.63±0.19% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.16±0.21% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.12±0.09% ID/g) was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (1.64±0.1% ID/g; P 111 In]-DOTA-K-E-[c(RGDfK)] 2 (1.52±0.04% ID/g; P v β 3 and tumor uptake. Insertion of lysine caused enhanced kidney retention; that of glutamic acid also resulted in enhanced retention in the kidneys. PEG 4 appeared to be the most suitable linker as compared with glutamic acid and lysine because it has the highest tumor-to-blood ratio and the lowest uptake in the kidney and liver

  11. Effect of secondary structure on the interactions of peptide T4 LYS (11-36) in mixtures of aqueous sodium chloride and 2,2,2,-Trifluoroethanol

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Camille O.; Spiegelberg, Susanne; Prausnitz, John M.; Blanch, Harvey W.

    2001-10-01

    The potential of mean force for protein-protein interactions is key to the development of a statistical-mechanical model for salt-induced protein precipitation and crystallization, and for understanding certain disease states, including cataract formation and {beta}-amyloid pathology in Alzheimer's disease. Fluorescence anisotropy provides a method for quantitative characterization of intermolecular interactions due to reversible association. Monomer-dimer equilibria for the peptide T4 LYS(11-36) were studied by fluorescence anisotropy. This peptide, derived from the {beta}-sheet region of the T4 lysozyme molecule, has the potential to form amyloid fibrils. 2,2,2-trifluoroethanol (TFE) induces a change in peptide secondary structure, and was used in aqueous solutions at concentrations from 0 to 50% (v/v) at 25 and 37 C to examine the role of peptide conformation on peptide-peptide interactions. The association constant for dimerization increased with rising TFE concentration and with falling temperature. The peptide-peptide potential of mean force was computed from these association constants. Circular-dichroism measurements showed that the secondary structure of the peptide plays an important role in these strong attractive interactions due to intermolecular hydrogen-bond formation and hydrophobic interactions.

  12. Structural characterization of the α-mating factor prepro-peptide for secretion of recombinant proteins in Pichia pastoris.

    Science.gov (United States)

    Chahal, Sabreen; Wei, Peter; Moua, Pachai; Park, Sung Pil James; Kwon, Janet; Patel, Arth; Vu, Anthony T; Catolico, Jason A; Tsai, Yu Fang Tina; Shaheen, Nadia; Chu, Tiffany T; Tam, Vivian; Khan, Zill-E-Huma; Joo, Hyun Henry; Xue, Liang; Lin-Cereghino, Joan; Tsai, Jerry W; Lin-Cereghino, Geoff P

    2017-01-20

    The methylotrophic yeast Pichia pastoris has been used extensively for expressing recombinant proteins because it combines the ease of genetic manipulation, the ability to provide complex posttranslational modifications and the capacity for efficient protein secretion. The most successful and commonly used secretion signal leader in Pichia pastoris has been the alpha mating factor (MATα) prepro secretion signal. However, limitations exist as some proteins cannot be secreted efficiently, leading to strategies to enhance secretion efficiency by modifying the secretion signal leader. Based on a Jpred secondary structure prediction and knob-socket modeling of tertiary structure, numerous deletions and duplications of the MATα prepro leader were engineered to evaluate the correlation between predicted secondary structure and the secretion level of the reporters horseradish peroxidase (HRP) and Candida antarctica lipase B. In addition, circular dichroism analyses were completed for the wild type and several mutant pro-peptides to evaluate actual differences in secondary structure. The results lead to a new model of MATα pro-peptide signal leader, which suggests that the N and C-termini of MATα pro-peptide need to be presented in a specific orientation for proper interaction with the cellular secretion machinery and for efficient protein secretion. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Probing the Gaseous Structure of a β-Hairpin Peptide with H/D Exchange and Electron Capture Dissociation.

    Science.gov (United States)

    Straus, Rita N; Jockusch, Rebecca A

    2017-02-01

    An improved understanding of the extent to which native protein structure is retained upon transfer to the gas phase promises to enhance biological mass spectrometry, potentially streamlining workflows and providing fundamental insights into hydration effects. Here, we investigate the gaseous conformation of a model β-hairpin peptide using gas-phase hydrogen-deuterium (H/D) exchange with subsequent electron capture dissociation (ECD). Global gas-phase H/D exchange levels, and residue-specific exchange levels derived from ECD data, are compared among the wild type 16-residue peptide GB1p and several variants. High protection from H/D exchange observed for GB1p, but not for a truncated version, is consistent with the retention of secondary structure of GB1p in the gas phase or its refolding into some other compact structure. Four alanine mutants that destabilize the hairpin in solution show levels of protection similar to that of GB1p, suggesting collapse or (re)folding of these peptides upon transfer to the gas phase. These results offer a starting point from which to understand how a key secondary structural element, the β-hairpin, is affected by transfer to the gas phase. This work also demonstrates the utility of a much-needed addition to the tool set that is currently available for the investigation of the gaseous conformation of biomolecules, which can be employed in the future to better characterize gaseous proteins and protein complexes. Graphical Abstract ᅟ.

  14. Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    2018-02-01

    Full Text Available The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.

  15. Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Bradley R.; Drake, Eric J.; Shi, Ce; Aldrich, Courtney C.; Gulick, Andrew M. (UMM); (HWMRI)

    2016-09-05

    Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived from understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa. These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain.

  16. Structural Variation Shapes the Landscape of Recombination in Mouse.

    Science.gov (United States)

    Morgan, Andrew P; Gatti, Daniel M; Najarian, Maya L; Keane, Thomas M; Galante, Raymond J; Pack, Allan I; Mott, Richard; Churchill, Gary A; de Villena, Fernando Pardo-Manuel

    2017-06-01

    Meiotic recombination is an essential feature of sexual reproduction that ensures faithful segregation of chromosomes and redistributes genetic variants in populations. Multiparent populations such as the Diversity Outbred (DO) mouse stock accumulate large numbers of crossover (CO) events between founder haplotypes, and thus present a unique opportunity to study the role of genetic variation in shaping the recombination landscape. We obtained high-density genotype data from [Formula: see text] DO mice, and localized 2.2 million CO events to intervals with a median size of 28 kb. The resulting sex-averaged genetic map of the DO population is highly concordant with large-scale (order 10 Mb) features of previously reported genetic maps for mouse. To examine fine-scale (order 10 kb) patterns of recombination in the DO, we overlaid putative recombination hotspots onto our CO intervals. We found that CO intervals are enriched in hotspots compared to the genomic background. However, as many as [Formula: see text] of CO intervals do not overlap any putative hotspots, suggesting that our understanding of hotspots is incomplete. We also identified coldspots encompassing 329 Mb, or [Formula: see text] of observable genome, in which there is little or no recombination. In contrast to hotspots, which are a few kilobases in size, and widely scattered throughout the genome, coldspots have a median size of 2.1 Mb and are spatially clustered. Coldspots are strongly associated with copy-number variant (CNV) regions, especially multi-allelic clusters, identified from whole-genome sequencing of 228 DO mice. Genes in these regions have reduced expression, and epigenetic features of closed chromatin in male germ cells, which suggests that CNVs may repress recombination by altering chromatin structure in meiosis. Our findings demonstrate how multiparent populations, by bridging the gap between large-scale and fine-scale genetic mapping, can reveal new features of the recombination

  17. Structural requirements and biological significance of interactions between peptides and the major histocompatibility complex

    DEFF Research Database (Denmark)

    Grey, H M; Buus, S; Colon, S

    1989-01-01

    Previous studies indicate that T cells recognize a complex between the major histocompatibility complex (MHC) restriction-element and peptide-antigen fragments. Two aspects of this complex formation are considered in this paper: (1) what is the nature of the specificity of the interactions that a...... of binding to Ia (i.e. determinant selection was operative), we found that about 40% of Ia-binding peptides were not immunogenic (i.e. there were also 'holes in the T-cell repertoire')....... responsiveness, we present data that suggest both mechanisms operate in concert with one another. Thus only about 30% of a collection of peptides that in sum represent the sequence of a protein molecule were found to bind to Ia. Although immunogenicity was restricted to those peptides that were capable...

  18. Ranalexin. A novel antimicrobial peptide from bullfrog (Rana catesbeiana) skin, structurally related to the bacterial antibiotic, polymyxin.

    Science.gov (United States)

    Clark, D P; Durell, S; Maloy, W L; Zasloff, M

    1994-04-08

    Antimicrobial peptides comprise a diverse class of molecules used in host defense by plants, insects, and animals. In this study we have isolated a novel antimicrobial peptide from the skin of the bullfrog, Rana catesbeiana. This 20 amino acid peptide, which we have termed Ranalexin, has the amino acid sequence: NH2-Phe-Leu-Gly-Gly-Leu-Ile-Lys-Ile-Val-Pro-Ala-Met-Ile-Cys-Ala-Val-Thr- Lys-Lys - Cys-COOH, and it contains a single intramolecular disulfide bond which forms a heptapeptide ring within the molecule. Structurally, Ranalexin resembles the bacterial antibiotic, polymyxin, which contains a similar heptapeptide ring. We have also cloned the cDNA for Ranalexin from a metamorphic R. catesbeiana tadpole cDNA library. Based on the cDNA sequence, it appears that Ranalexin is initially synthesized as a propeptide with a putative signal sequence and an acidic amino acid-rich region at its amino-terminal end. Interestingly, the putative signal sequence of the Ranalexin cDNA is strikingly similar to the signal sequence of opioid peptide precursors isolated from the skin of the South American frogs Phyllomedusa sauvagei and Phyllomedusa bicolor. Northern blot analysis and in situ hybridization experiments demonstrated that Ranalexin mRNA is first expressed in R. catesbeiana skin at metamorphosis and continues to be expressed into adulthood.

  19. The peptide-receptive transition state of MHC-1 molecules: Insight from structure and molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Robinson H.; Mage, M.; Dolan, M.; Wang, R.; Boyd, L.; Revilleza, M.; Natarajan, K.; Myers, N.; Hansen, T.; Margulies, D.

    2012-05-01

    MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I-restricted CD8(+) T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 3(10) helix that flips from an exposed 'open' position in the PR transition state to a 'closed' position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46-53 of murine H-2L(d) MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.

  20. Variations in Crust and Upper Mantle Structure Beneath Diverse Geologic Provinces in Asia

    National Research Council Canada - National Science Library

    Schwartz, Susan H

    1997-01-01

    This report presents results of a two year effort to determine crust and mantle lithospheric structure beneath Eurasia and to explore the effects that structural variations have on regional wave propagation...

  1. Practice variation in the structure of stroke rehabilitation in four rehabilitation centres in the Netherlands

    NARCIS (Netherlands)

    Groeneveld, Iris F.; Meesters, Jorit J. L.; Arwert, Henk J.; Roux-Otter, Nienke; Ribbers, Gerard M.; van Bennekom, Coen A. M.; Goossens, Paulien H.; Vliet Vlieland, Thea P. M.

    2016-01-01

    To describe practice variation in the structure of stroke rehabilitation in 4 specialized multidisciplinary rehabilitation centres in the Netherlands. A multidisciplinary expert group formulated a set of 23 elements concerning the structure of inpatient and outpatient stroke rehabilitation,

  2. Simultaneous Structural Variation Discovery in Multiple Paired-End Sequenced Genomes

    Science.gov (United States)

    Hormozdiari, Fereydoun; Hajirasouliha, Iman; McPherson, Andrew; Eichler, Evan E.; Sahinalp, S. Cenk

    Next generation sequencing technologies have been decreasing the costs and increasing the world-wide capacity for sequence production at an unprecedented rate, making the initiation of large scale projects aiming to sequence almost 2000 genomes [1]. Structural variation detection promises to be one of the key diagnostic tools for cancer and other diseases with genomic origin. In this paper, we study the problem of detecting structural variation events in two or more sequenced genomes through high throughput sequencing . We propose to move from the current model of (1) detecting genomic variations in single next generation sequenced (NGS) donor genomes independently, and (2) checking whether two or more donor genomes indeed agree or disagree on the variations (in this paper we name this framework Independent Structural Variation Discovery and Merging - ISV&M), to a new model in which we detect structural variation events among multiple genomes simultaneously.

  3. Spatio-temporal variations in phytoplankton community structure in ...

    African Journals Online (AJOL)

    OMARI

    2013-09-06

    Sep 6, 2013 ... estimating potential fish yield (Descy et al., 2005), .... populations have been conducted in open waters Lake ... Victoria basin Kenya which was stratified in terms of altitude .... Mean monthly variation of surface water pH values in small water bodies ..... Although there was optimal temperature, pH, D.O.

  4. Sensitivity of ab Initio vs Empirical Methods in Computing Structural Effects on NMR Chemical Shifts for the Example of Peptides.

    Science.gov (United States)

    Sumowski, Chris Vanessa; Hanni, Matti; Schweizer, Sabine; Ochsenfeld, Christian

    2014-01-14

    The structural sensitivity of NMR chemical shifts as computed by quantum chemical methods is compared to a variety of empirical approaches for the example of a prototypical peptide, the 38-residue kaliotoxin KTX comprising 573 atoms. Despite the simplicity of empirical chemical shift prediction programs, the agreement with experimental results is rather good, underlining their usefulness. However, we show in our present work that they are highly insensitive to structural changes, which renders their use for validating predicted structures questionable. In contrast, quantum chemical methods show the expected high sensitivity to structural and electronic changes. This appears to be independent of the quantum chemical approach or the inclusion of solvent effects. For the latter, explicit solvent simulations with increasing number of snapshots were performed for two conformers of an eight amino acid sequence. In conclusion, the empirical approaches neither provide the expected magnitude nor the patterns of NMR chemical shifts determined by the clearly more costly ab initio methods upon structural changes. This restricts the use of empirical prediction programs in studies where peptide and protein structures are utilized for the NMR chemical shift evaluation such as in NMR refinement processes, structural model verifications, or calculations of NMR nuclear spin relaxation rates.

  5. Crystal Structure of Glucagon-like Peptide-1 in Complex with the Extracellular Domain of the Glucagon-like Peptide-1 Receptor*

    Science.gov (United States)

    Underwood, Christina Rye; Garibay, Patrick; Knudsen, Lotte Bjerre; Hastrup, Sven; Peters, Günther H.; Rudolph, Rainer; Reedtz-Runge, Steffen

    2010-01-01

    GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic β-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full agonist with similar affinity and potency for the GLP-1 receptor. We recently solved the crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4(9–39). Interestingly, the isolated extracellular domain binds exendin-4 with much higher affinity than the endogenous agonist GLP-1. Here, we have solved the crystal structure of the extracellular domain in complex with GLP-1 to 2.1 Åresolution. The structure shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extracellular domain, but certain residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is a kinked but continuous α-helix from Thr13 to Val33 when bound to the extracellular domain. We supplemented the crystal structure with site-directed mutagenesis to link the structural information of the isolated extracellular domain with the binding properties of the full-length receptor. The data support the existence of differences in the binding modes of GLP-1 and exendin-4 on the full-length GLP-1 receptor. PMID:19861722

  6. Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor.

    Science.gov (United States)

    Underwood, Christina Rye; Garibay, Patrick; Knudsen, Lotte Bjerre; Hastrup, Sven; Peters, Günther H; Rudolph, Rainer; Reedtz-Runge, Steffen

    2010-01-01

    GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic beta-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full agonist with similar affinity and potency for the GLP-1 receptor. We recently solved the crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4(9-39). Interestingly, the isolated extracellular domain binds exendin-4 with much higher affinity than the endogenous agonist GLP-1. Here, we have solved the crystal structure of the extracellular domain in complex with GLP-1 to 2.1 Aresolution. The structure shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extracellular domain, but certain residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is a kinked but continuous alpha-helix from Thr(13) to Val(33) when bound to the extracellular domain. We supplemented the crystal structure with site-directed mutagenesis to link the structural information of the isolated extracellular domain with the binding properties of the full-length receptor. The data support the existence of differences in the binding modes of GLP-1 and exendin-4 on the full-length GLP-1 receptor.

  7. Membrane interactions of a self-assembling model peptide that mimics the self-association, structure and toxicity of Aβ(1-40)

    Science.gov (United States)

    Salay, Luiz C.; Qi, Wei; Keshet, Ben; Tamm, Lukas K.; Fernandez, Erik J.

    2013-01-01

    β-amyloid peptide (Aβ) is a primary protein component of senile plaques in Alzheimer’s disease (AD) and plays an important, but not fully understood role in neurotoxicity. Model peptides with the demonstrated ability to mimic the structural and toxicity behavior of Aβ could provide a means to evaluate the contributions to toxicity that are common to self–associating peptides from many disease states. In this work, we have studied the peptide-membrane interactions of a model β-sheet peptide, P11-2 (CH3CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe-Glu-Gln-Gln-NH2), by fluorescence, infrared spectroscopy, and hydrogen-deuterium exchange. Like Aβ(1-40), the peptide is toxic, and conditions which produce intermediate oligomers show higher toxicity against cells than either monomeric forms or higher aggregates of the peptide. Further, P11-2 also binds to both zwitterionic (POPC) and negatively charged (POPC:POPG) liposomes, acquires a partial β-sheet conformation in presence of lipid, and is protected against deuterium exchange in the presence of lipids. The results show that a simple rationally designed model β-sheet peptide recapitulates many important features of Aβ peptide structure and function, reinforcing the idea that toxicity arises, at least in part, from a common mode of action on membranes that is independent of specific aspects of the amino acid sequence. Further studies of such well-behaved model peptide systems will facilitate the investigation of the general principles that govern the molecular interactions of aggregation-prone disease-associated peptides with cell and/or membrane surfaces. PMID:19393615

  8. Structure, synthesis, and molecular cloning of dermaseptins B, a family of skin peptide antibiotics.

    Science.gov (United States)

    Charpentier, S; Amiche, M; Mester, J; Vouille, V; Le Caer, J P; Nicolas, P; Delfour, A

    1998-06-12

    Analysis of antimicrobial activities that are present in the skin secretions of the South American frog Phyllomedusa bicolor revealed six polycationic (lysine-rich) and amphipathic alpha-helical peptides, 24-33 residues long, termed dermaseptins B1 to B6, respectively. Prepro-dermaseptins B all contain an almost identical signal peptide, which is followed by a conserved acidic propiece, a processing signal Lys-Arg, and a dermaseptin progenitor sequence. The 22-residue signal peptide plus the first 3 residues of the acidic propiece are encoded by conserved nucleotides encompassed by the first coding exon of the dermaseptin genes. The 25-residue amino-terminal region of prepro-dermaseptins B shares 50% identity with the corresponding region of precursors for D-amino acid containing opioid peptides or for antimicrobial peptides originating from the skin of distantly related frog species. The remarkable similarity found between prepro-proteins that encode end products with strikingly different sequences, conformations, biological activities and modes of action suggests that the corresponding genes have evolved through dissemination of a conserved "secretory cassette" exon.

  9. NMR structures of anti-HIV D-peptides derived from the N-terminus of viral chemokine vMIP-II

    International Nuclear Information System (INIS)

    Mori, Mayuko; Liu Dongxiang; Kumar, Santosh; Huang Ziwei

    2005-01-01

    The viral macrophage inflammatory protein-II (vMIP-II) encoded by Kaposi's sarcoma-associated herpesvirus has unique biological activities in that it blocks the cell entry by several different human immunodeficiency virus type 1 (HIV-1) strains via chemokine receptors including CXCR4 and CCR5. In this paper, we report the solution structure of all-D-amino acid peptides derived from the N-terminus of vMIP-II, which have been shown to have strong CXCR4 binding activity and potently inhibit HIV-1 entry via CXCR4, by using long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy experiments. Both of all-D-peptides vMIP-II (1-10) and vMIP-II (1-21), which are designated as DV3 and DV1, respectively, have higher CXCR4 binding ability than their L-peptide counterparts. They are partially structured in aqueous solution, displaying a turn-like structure over residues 5-8. The small temperature coefficients of His-6 amide proton for both peptides also suggest the formation of a small hydrophobic pocket centered on His-6. The structural features of DV3 are very similar to the reported solution structure of all-L-peptide vMIP-II (1-10) [M.P. Crump, E. Elisseeva, J. Gong, I. Clark-Lewis, B.D. Sykes, Structure/function of human herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10), FEBS Lett. 489 (2001) 171], which is consistent with the notion that D- and L-enantiomeric peptides can adopt mirror image conformations. The NMR structures of the D-peptides provide a structural basis to understand their mechanism of action and design new peptidomimetic analogs to further explore the structure-activity relationship of D-peptide ligand binding to CXCR4

  10. Control over Structure and Function of Peptide Amphiphile Supramolecular Assemblies through Molecular Design and Energy Landscapes

    Science.gov (United States)

    Tantakitti, Faifan

    Supramolecular chemistry is a powerful tool to create a material of a defined structure with tunable properties. This strategy has led to catalytically active, bioactive, and environment-responsive materials, among others, that are valuable in applications ranging from sensor technology to energy and medicine. Supramolecular polymers formed by peptide amphiphiles (PAs) have been especially relevant in tissue regeneration due to their ability to form biocompatible structures and mimic many important signaling molecules in biology. These supramolecular polymers can form nanofibers that create networks which mimic natural extracellular matrices. PA materials have been shown to induce growth of blood vessels, bone, cartilage, and nervous tissue, among others. The work described in this thesis not only studied the relationship between molecular structure and functions of PA assemblies, but also uncovered a powerful link between the energy landscape of their supramolecular self-assembly and the ability of PA materials to interact with cells. In chapter 2, it is argued that fabricating fibrous nanostructures with defined mechanical properties and decoration with bioactive molecules is not sufficient to create a material that can effectively communicate with cells. By systemically placing the fibronectin-derived RGDS epitope at increasing distances from the surface of PA nanofibers through a linker of one to five glycine residues, integrin-mediated RGDS signaling was enhanced. The results suggested that the spatial presentation of an epitope on PA nanofibers strongly influences the bioactivity of the PA substrates. In further improving functionality of a PA-based scaffold to effectively direct cell growth and differentiation, chapter 3 explored the use of a cell microcarrier to compartmentalize and simultaneously tune insoluble and soluble signals in a single matrix. PA nanofibers were incorporated at the surface of the microcarrier in order to promote cell adhesion, while

  11. Syntheses and structures of technetium(V) and rhenium(V) oxo complexes of peptide having KYC-sequence

    International Nuclear Information System (INIS)

    Takayama, T.; Suzuki, K.; Sekine, T.; Kudo, H.

    2000-01-01

    Technetium(V) and rhenium(V) oxo complexes of a peptide having a KYC-sequence such as KYCAR (H 3 L 5 ) and KYCAREPPTRTNAYQGQG-NH 2 (H 3 L 18 ) were synthesized, and structures of the complexes were characterized by spectroscopic techniques. All of the complexes were synthesized by the ligand exchange reaction of [(n-C 4 H 9 ) 4 N][MOCl 4 ] (M = 99 Tc, Re) with peptide in methanol or dimethylformamide solution. These complexes have a square pyramidal structure with an oxo ligand at the apical position. The peptide is coordinated to a metal atom through N amine of lysine. S thiol of cysteine, and N amide of tyrosine and cysteine in the equatorial plane. A lysine (CH 2 ) 4 NH 2 group of the L 5 ligand has the syn conformation with respect to metal-oxo bonding in the complex. The syn isomer was selectively formed in the ligand exchange reaction. The conversion of the syn isomer to the anti isomer was observed only for syn-[ReO(L 5 )], in which the coordination of water to the trans position of the oxo ligand was involved. (orig.)

  12. Syntheses and structures of technetium(V) and rhenium(V) oxo complexes of peptide having KYC-sequence

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, T.; Suzuki, K.; Sekine, T.; Kudo, H. [Dept. of Chemistry, Tohoku Univ., Sendai (Japan)

    2000-07-01

    Technetium(V) and rhenium(V) oxo complexes of a peptide having a KYC-sequence such as KYCAR (H{sub 3}L{sup 5}) and KYCAREPPTRTNAYQGQG-NH{sub 2} (H{sub 3}L{sup 18}) were synthesized, and structures of the complexes were characterized by spectroscopic techniques. All of the complexes were synthesized by the ligand exchange reaction of [(n-C{sub 4}H{sub 9}){sub 4}N][MOCl{sub 4}] (M = {sup 99}Tc, Re) with peptide in methanol or dimethylformamide solution. These complexes have a square pyramidal structure with an oxo ligand at the apical position. The peptide is coordinated to a metal atom through N{sub amine} of lysine. S{sub thiol} of cysteine, and N{sub amide} of tyrosine and cysteine in the equatorial plane. A lysine (CH{sub 2}){sub 4}NH{sub 2} group of the L{sup 5} ligand has the syn conformation with respect to metal-oxo bonding in the complex. The syn isomer was selectively formed in the ligand exchange reaction. The conversion of the syn isomer to the anti isomer was observed only for syn-[ReO(L{sup 5})], in which the coordination of water to the trans position of the oxo ligand was involved. (orig.)

  13. Variations analysis of the Society's preference structure regarding environmental issues

    International Nuclear Information System (INIS)

    Angel S, Enrique; Zambrano B, Ana Maria

    2005-01-01

    Society's preference structure regarding environmental issues is understood as the relative importance the society gives to various topics that collectively conform the environmental issues. Based on the hypothesis that this structure behavior and its definition vary with time, proposals are presented related to the concepts and a working plan allowing performing the structure's dynamic analysis. A method is described to gather information based on the systematic reading of a nation wide newspaper during a period time. A comparison is done between the resulting structure and several aspects as the environmental legislation, government plans and summits and environmental milestones

  14. Structure-Based Design of Peptidic Inhibitors of the Interaction between CC Chemokine Ligand 5 (CCL5) and Human Neutrophil Peptides 1 (HNP1)

    NARCIS (Netherlands)

    Wichapong, Kanin; Alard, Jean-Eric; Ortega-Gomez, Almudena; Weber, Christian; Hackeng, Tilman M.; Soehnlein, Oliver; Nicolaes, Gerry A. F.

    2016-01-01

    Protein-protein interactions (PPIs) are receiving increasing interest, much sparked by the realization that they represent druggable targets. Recently, we successfully developed a peptidic inhibitor, RRYGTSKYQ ("SKY" peptide), that shows high potential in vitro and in vivo to interrupt a PPI between

  15. Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex

    DEFF Research Database (Denmark)

    Lou, Chenguang; Christensen, Niels Johan; Martos Maldonado, Manuel Cristo

    2017-01-01

    by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne-azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex......, small-angle X-ray scattering (SAXS), and molecular modeling. Stabilizing cooperativity was observed between the trimeric peptide and the oligonucleotide triplex domains, and the overall molecular size (ca. 12nm) in solution was revealed to be independent of concentration. The topological folding...

  16. Uncertainty and Variation of Vibration in Lightweight Structures

    DEFF Research Database (Denmark)

    Dickow, Kristoffer Ahrens

    2012-01-01

    Multi-family dwellings and offices build from lightweight materials are becoming a cost efficient and environmentally friendly alternative to traditional heavy structures.......Multi-family dwellings and offices build from lightweight materials are becoming a cost efficient and environmentally friendly alternative to traditional heavy structures....

  17. Morphodynamics structures induced by variations of the channel width

    Science.gov (United States)

    Duro, Gonzalo; Crosato, Alessandra; Tassi, Pablo

    2014-05-01

    In alluvial channels, forcing effects, such as a longitudinally varying width, can induce the formation of steady bars (Olesen, 1984). The type of bars that form, such as alternate, central or multiple, will mainly depend on the local flow width-to-depth ratio and on upstream conditions (Struiksma et al., 1985). The effects on bar formation of varying the channel width received attention only recently and investigations, based on flume experiments and mathematical modelling, are mostly restricted to small longitudinal sinusoidal variations of the channel width (e.g. Repetto et al., 2002; Wu and Yeh, 2005, Zolezzi et al., 2012; Frascati and Lanzoni, 2013). In this work, we analyze the variations in equilibrium bed topography in a longitudinal width-varying channel with characteristic scales of the Waal River (The Netherlands) using two different 2D depth-averaged morphodynamic models, one based on the Delft3D code and one on Telemac-Mascaret system. In particular, we explore the effects of changing the wavelength of sinusoidal width variations in a straight channel, focusing on the effects of the spatial lag between bar formation and forcing that is observed in numerical models and laboratory experiments (e.g. Crosato et al, 2011). We extend the investigations to finite width variations in which longitudinal changes of the width-to-depth ratio are such that they may affect the type of bars that become unstable (alternate, central or multiple bars). Numerical results are qualitatively validated with field observations and the resulting morphodynamic pattern is compared with the physics-based predictor of river bar modes by Crosato and Mosselman (2009). The numerical models are finally used to analyse the experimental conditions of Wu and Yeh (2005). The study should be seen as merely exploratory. The aim is to investigate possible approaches for future research aiming at assessing the effects of artificial river widening and narrowing to control bar formation in

  18. Phylogenetic community structure: temporal variation in fish assemblage

    OpenAIRE

    Santorelli, Sergio; Magnusson, William; Ferreira, Efrem; Caramaschi, Erica; Zuanon, Jansen; Amadio, Sidnéia

    2014-01-01

    Hypotheses about phylogenetic relationships among species allow inferences about the mechanisms that affect species coexistence. Nevertheless, most studies assume that phylogenetic patterns identified are stable over time. We used data on monthly samples of fish from a single lake over 10 years to show that the structure in phylogenetic assemblages varies over time and conclusions depend heavily on the time scale investigated. The data set was organized in guild structures and temporal scales...

  19. Structure-activity relationship of CART (cocaine- and amphetamine-regulated transcript) peptide fragments

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Hlaváček, Jan; Blokešová, Darja; Kowalczyk, W.; Elbert, Tomáš; Šanda, Miloslav; Blechová, Miroslava; Železná, Blanka; Slaninová, Jiřina; Maletínská, Lenka

    2007-01-01

    Roč. 28, č. 10 (2007), s. 1945-1953 ISSN 0196-9781 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : CART peptide * fragments * binding * PC12 cells Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.368, year: 2007

  20. Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin

    NARCIS (Netherlands)

    Haney, E.F.; Nazmi, K.; Bolscher, J.G.M.; Vogel, H.J.

    2012-01-01

    Lactoferricin and lactoferrampin are two antimicrobial peptides found in the N-terminal lobe of bovine lactoferrin with broad spectrum antimicrobial activity against a range of Gram-positive and Gram-negative bacteria as well as Candida albicans. A heterodimer comprised of lactoferrampin joined to a

  1. Biofilms from Klebsiella pneumoniae: Matrix Polysaccharide Structure and Interactions with Antimicrobial Peptides.

    Science.gov (United States)

    Benincasa, Monica; Lagatolla, Cristina; Dolzani, Lucilla; Milan, Annalisa; Pacor, Sabrina; Liut, Gianfranco; Tossi, Alessandro; Cescutti, Paola; Rizzo, Roberto

    2016-08-10

    Biofilm matrices of two Klebsiella pneumoniae clinical isolates, KpTs101 and KpTs113, were investigated for their polysaccharide composition and protective effects against antimicrobial peptides. Both strains were good biofilm producers, with KpTs113 forming flocs with very low adhesive properties to supports. Matrix exopolysaccharides were isolated and their monosaccharide composition and glycosidic linkage types were defined. KpTs101 polysaccharide is neutral and composed only of galactose, in both pyranose and furanose ring configurations. Conversely, KpTs113 polysaccharide is anionic due to glucuronic acid units, and also contains glucose and mannose residues. The susceptibility of the two strains to two bovine cathelicidin antimicrobial peptides, BMAP-27 and Bac7(1-35), was assessed using both planktonic cultures and biofilms. Biofilm matrices exerted a relevant protection against both antimicrobials, which act with quite different mechanisms. Similar protection was also detected when antimicrobial peptides were tested against planktonic bacteria in the presence of the polysaccharides extracted from KpTs101 and KpTs113 biofilms, suggesting sequestering adduct formation with antimicrobials. Circular dichroism experiments on BMAP-27 in the presence of increasing amounts of either polysaccharide confirmed their ability to interact with the peptide and induce an α-helical conformation.

  2. Vibrational spectral simulation for peptides of mixed secondary structure: Method comparisons with the Trpzip model hairpin

    Czech Academy of Sciences Publication Activity Database

    Bouř, Petr; Keiderling, T. A.

    2005-01-01

    Roč. 109, - (2005), 23687-23697 ISSN 1089-5647 R&D Projects: GA AV ČR(CZ) IAA4055104 Grant - others:NSF(US) CHE03-16014 Institutional research plan: CEZ:AV0Z40550506 Keywords : VCD * trpzin model hairpin * peptides Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.679, year: 2003

  3. Structural features of peptoid-peptide hybrids in lipid-water interfaces

    DEFF Research Database (Denmark)

    Uggerhøj, Lars Erik; Munk, Jens K.; Hansen, Paul Robert

    2014-01-01

    The inclusion of peptoid monomers into antimicrobial peptides (AMPs) increases their proteolytic resistance, but introduces conformational flexibility (reduced hydrogen bonding ability and cis/trans isomerism). We here use NMR spectroscopy to answer how the insertion of a peptoid monomer influenc...

  4. Structural and antimicrobial properties of human pre-elafin/trappin-2 and derived peptides against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Gagné Stéphane M

    2010-10-01

    Full Text Available Abstract Background Pre-elafin/trappin-2 is a human innate defense molecule initially described as a potent inhibitor of neutrophil elastase. The full-length protein as well as the N-terminal "cementoin" and C-terminal "elafin" domains were also shown to possess broad antimicrobial activity, namely against the opportunistic pathogen P. aeruginosa. The mode of action of these peptides has, however, yet to be fully elucidated. Both domains of pre-elafin/trappin-2 are polycationic, but only the structure of the elafin domain is currently known. The aim of the present study was to determine the secondary structures of the cementoin domain and to characterize the antibacterial properties of these peptides against P. aeruginosa. Results We show here that the cementoin domain adopts an α-helical conformation both by circular dichroism and nuclear magnetic resonance analyses in the presence of membrane mimetics, a characteristic shared with a large number of linear polycationic antimicrobial peptides. However, pre-elafin/trappin-2 and its domains display only weak lytic properties, as assessed by scanning electron micrography, outer and inner membrane depolarization studies with P. aeruginosa and leakage of liposome-entrapped calcein. Confocal microscopy of fluorescein-labeled pre-elafin/trappin-2 suggests that this protein possesses the ability to translocate across membranes. This correlates with the finding that pre-elafin/trappin-2 and elafin bind to DNA in vitro and attenuate the expression of some P. aeruginosa virulence factors, namely the biofilm formation and the secretion of pyoverdine. Conclusions The N-terminal cementoin domain adopts α-helical secondary structures in a membrane mimetic environment, which is common in antimicrobial peptides. However, unlike numerous linear polycationic antimicrobial peptides, membrane disruption does not appear to be the main function of either cementoin, elafin or full-length pre-elafin/trappin-2 against

  5. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  6. Chemical construction and structural permutation of potent cytotoxin polytheonamide B: discovery of artificial peptides with distinct functions.

    Science.gov (United States)

    Itoh, Hiroaki; Inoue, Masayuki

    2013-07-16

    Polytheonamide B (1), isolated from the marine sponge Theonella swinhoei, is a posttranslationally modified ribosomal peptide (MW 5030 Da) that displays extraordinary cytotoxicity. Among its 48 amino acid residues, this peptide includes a variety D- and L-amino acids that do not occur in proteins, and the chiralities of these amino acids alternate in sequence. These structural features induce the formation of a stable β6.3-helix, giving rise to a tubular structure of over 4 nm in length. In the biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. In this Account, we discuss the construction and structural permutations of this potent cytotoxin. First we describe the 161-step chemical construction of this unusual peptide 1. By developing a synthetic route to 1, we established the chemical basis for subsequent SAR studies to pinpoint the proteinogenic and nonproteinogenic building blocks within the molecule that confer its toxicity and channel function. Using fully synthetic 1, we generated seven analogues with point mutations, and studies of their activity revealed the importance of the N-terminal moiety. Next, we simplified the structure of 1 by substituting six amino acid residues of 1 to design a more synthetically accessible analogue 9. This dansylated polytheonamide mimic 9 was synthesized in 127 total steps, and we evaluated its function to show that it can emulate the toxic and ion channel activities of 1 despite its multiple structural modifications. Finally, we applied a highly automated synthetic route to 48-mer 9 to generate 13 substructures of 27-39-mers. The 37-mer 12 exhibited nanomolar level toxicity through a potentially distinct mode of action from 1 and 9. The SAR studies of polytheonamide B and the 21 artificial analogues have deepened our understanding of the precise structural requirements for the biological functions of 1. They have also led to the discovery of

  7. Structural changes of the ligand and of the receptor alters the receptor preference for neutrophil activating peptides starting with a 3 formylmethionyl group

    DEFF Research Database (Denmark)

    Forsman, Huamei; Winther, Malene; Gabl, Michael

    2015-01-01

    Pathogenic Staphylococcus aureus strains produce N-formylmethionyl containing peptides, of which the tetrapeptide fMIFL is a potent activator of the neutrophil formyl peptide receptor 1 (FPR1) and the PSMα2 peptide is a potent activator of the closely related FPR2. Variants derived from these two...... peptide activators were used to disclose the structural determinants for receptor interaction. Removal of five amino acids from the C-terminus of PSMα2 gave rise to a peptide that had lost the receptor-independent neutrophil permeabilizing effect, whereas neutrophil activation capacity as well as its...... preference for FPR2 was retained. Shorter peptides, PSMα21–10 and PSMα21–5, activate neutrophils, but the receptor preference for these peptides was switched to FPR1. The fMIFL-PSM5–16 peptide, in which the N-terminus of PSMα21–16 was replaced by the sequence fMIFL, was a dual agonist for FPR1/FPR2, whereas...

  8. Solution structure of the 45-residue MgATP-binding peptide of adenylate kinase as examined by 2-D NMR, FTIR, and CD spectroscopy

    International Nuclear Information System (INIS)

    Fry, D.C.; Byler, D.M.; Susi, H.; Brown, M.; Kuby, S.A.; Mildvan, A.S.

    1988-01-01

    The structure of a synthetic peptide corresponding to residues 1-45 of rabbit muscle adenylate kinase has been studied in aqueous solution by two-dimensional NMR, FTIR, and CD spectroscopy. This peptide, which binds MgATP and is believed to represent most of the MgATP-binding site of the enzyme, appears to maintain a conformation similar to that of residues 1-45 in the X-ray structure of intact porcine adenylate kinase, with 42% of the residues of the peptide showing NOEs indicative of phi and psi angles corresponding to those found in the protein. The NMR studies suggest that the peptide is composed of two helical regions of residues 4-7 and 23-29, and three stretches of β-strand at residues 8-15, 30-32, and 35-40, yielding an overall secondary structure consisting of 24% α-helix, 38% β-structure, and 38% aperiodic. Although the resolution-enhanced amide I band of the peptide FTIR spectrum is broad and rather featureless, possible due to disorder, it can be fit by using methods developed on well-characterized globular proteins. The CD spectrum is best fit by assuming the presence of at most 13% α-helix in the peptide, 24 +/- 2% β-structure, and 66 +/- 4% aperiodic. The inability of the high-frequency FTIR and CD methods to detect helices in the amount found by NMR may result from the short helical lengths as well as from static and dynamic disorder in the peptide. Upon binding of MgATP, numerous conformation changes in the backbone of the peptide are detected by NMR, with smaller alterations in the overall secondary structure as assess by CD

  9. Self-consistent field variational cellular method as applied to the band structure calculation of sodium

    International Nuclear Information System (INIS)

    Lino, A.T.; Takahashi, E.K.; Leite, J.R.; Ferraz, A.C.

    1988-01-01

    The band structure of metallic sodium is calculated, using for the first time the self-consistent field variational cellular method. In order to implement the self-consistency in the variational cellular theory, the crystal electronic charge density was calculated within the muffin-tin approximation. The comparison between our results and those derived from other calculations leads to the conclusion that the proposed self-consistent version of the variational cellular method is fast and accurate. (author) [pt

  10. Evolutionary rate variation and RNA secondary structure prediction

    DEFF Research Database (Denmark)

    Knudsen, B.; Andersen, E.S.; Damgaard, C.

    2004-01-01

    Predicting RNA secondary structure using evolutionary history can be carried out by using an alignment of related RNA sequences with conserved structure. Accurately determining evolutionary substitution rates for base pairs and single stranded nucleotides is a concern for methods based on this type...... by applying rates derived from tRNA and rRNA to the prediction of the much more rapidly evolving 5'-region of HIV-1. We find that the HIV-1 prediction is in agreement with experimental data, even though the relative evolutionary rate between A and G is significantly increased, both in stem and loop regions...

  11. Structural genomic variation in childhood epilepsies with complex phenotypes

    DEFF Research Database (Denmark)

    Helbig, Ingo; Swinkels, Marielle E M; Aten, Emmelien

    2014-01-01

    of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened.......9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more...

  12. Membrane-Active Epithelial Keratin 6A Fragments (KAMPs) Are Unique Human Antimicrobial Peptides with a Non-αβ Structure

    Science.gov (United States)

    Lee, Judy T. Y.; Wang, Guangshun; Tam, Yu Tong; Tam, Connie

    2016-01-01

    Antibiotic resistance is a pressing global health problem that threatens millions of lives each year. Natural antimicrobial peptides and their synthetic derivatives, including peptoids and peptidomimetics, are promising candidates as novel antibiotics. Recently, the C-terminal glycine-rich fragments of human epithelial keratin 6A were found to have bactericidal and cytoprotective activities. Here, we used an improved 2-dimensional NMR method coupled with a new protocol for structural refinement by low temperature simulated annealing to characterize the solution structure of these kerain-derived antimicrobial peptides (KAMPs). Two specific KAMPs in complex with membrane mimicking sodium dodecyl sulfate (SDS) micelles displayed amphipathic conformations with only local bends and turns, and a central 10-residue glycine-rich hydrophobic strip that is central to bactericidal activity. To our knowledge, this is the first report of non-αβ structure for human antimicrobial peptides. Direct observation of Staphylococcus aureus and Pseudomonas aeruginosa by scanning and transmission electron microscopy showed that KAMPs deformed bacterial cell envelopes and induced pore formation. Notably, in competitive binding experiments, KAMPs demonstrated binding affinities to LPS and LTA that did not correlate with their bactericidal activities, suggesting peptide-LPS and peptide-LTA interactions are less important in their mechanisms of action. Moreover, immunoprecipitation of KAMPs-bacterial factor complexes indicated that membrane surface lipoprotein SlyB and intracellular machineries NQR sodium pump and ribosomes are potential molecular targets for the peptides. Results of this study improve our understanding of the bactericidal function of epithelial cytokeratin fragments, and highlight an unexplored class of human antimicrobial peptides, which may serve as non-αβ peptide scaffolds for the design of novel peptide-based antibiotics. PMID:27891122

  13. Membrane-Active Epithelial Keratin 6A Fragments (KAMPs Are Unique Human Antimicrobial Peptides with a Non-αβ Structure

    Directory of Open Access Journals (Sweden)

    Judy Tsz Ying Lee

    2016-11-01

    Full Text Available Antibiotic resistance is a pressing global health problem that threatens millions of lives each year. Natural antimicrobial peptides and their synthetic derivatives, including peptoids and peptidomimetics, are promising candidates as novel antibiotics. Recently, the C-terminal glycine-rich fragments of human epithelial keratin 6A were found to have bactericidal and cytoprotective activities. Here, we used an improved 2-dimensional NMR method coupled with a new protocol for structural refinement by low temperature simulated annealing to characterize the solution structure of these kerain-derived antimicrobial peptides (KAMPs. Two specific KAMPs in complex with membrane mimicking sodium dodecyl sulfate (SDS micelles displayed amphipathic conformations with only local bends and turns, and a central 10-residue glycine-rich hydrophobic strip that is central to bactericidal activity. To our knowledge, this is the first report of non-αβ structure for human antimicrobial peptides. Direct observation of Staphylococcus aureus and Pseudomonas aeruginosa by scanning and transmission electron microscopy showed that KAMPs deformed bacterial cell envelopes and induced pore formation. Notably, in competitive binding experiments, KAMPs demonstrated binding affinities to LPS and LTA that did not correlate with their bactericidal activities, suggesting peptide-LPS and peptide-LTA interactions are less important in their mechanisms of action. Moreover, immunoprecipitation of KAMPs-bacterial factor complexes indicated that membrane surface lipoprotein SlyB and intracellular machineries NQR sodium pump and ribosomes are potential molecular targets for the peptides. Results of this study improve our understanding of the bactericidal function of epithelial cytokeratin fragments, and highlight an unexplored class of human antimicrobial peptides, which may serve as non-αβ peptide scaffolds for the design of novel peptide-based antibiotics.

  14. Crystal structures of two peptide-HLA-B*1501 complexes; structural characterization of the HLA-B62 supertype

    DEFF Research Database (Denmark)

    Roder, G; Blicher, Thomas; Justesen, Sune Frederik Lamdahl

    2006-01-01

    MHC class I molecules govern human cytotoxic T cell responses. Their specificity determines which peptides they sample from the intracellular protein environment and then present to human cytotoxic T cells. More than 1100 different MHC class I proteins have been found in human populations...

  15. Structure Variation from One-Dimensional Chain to Three ...

    Indian Academy of Sciences (India)

    WEN-XUAN LI, XIAO-MIN GU, WEN-LI ZHANG and LIANG NI. School of Chemistry ... Compound 1 possesses one-dimensional chain structure, and expands into ..... sis of fine chemicals and pharmaceuticals.30 The results were summarized ...

  16. Variation in the helical structure of native collagen.

    Directory of Open Access Journals (Sweden)

    Joseph P R O Orgel

    Full Text Available The structure of collagen has been a matter of curiosity, investigation, and debate for the better part of a century. There has been a particularly productive period recently, during which much progress has been made in better describing all aspects of collagen structure. However, there remain some questions regarding its helical symmetry and its persistence within the triple-helix. Previous considerations of this symmetry have sometimes confused the picture by not fully recognizing that collagen structure is a highly complex and large hierarchical entity, and this affects and is effected by the super-coiled molecules that make it. Nevertheless, the symmetry question is not trite, but of some significance as it relates to extracellular matrix organization and cellular integration. The correlation between helical structure in the context of the molecular packing arrangement determines which parts of the amino acid sequence of the collagen fibril are buried or accessible to the extracellular matrix or the cell. In this study, we concentrate primarily on the triple-helical structure of fibrillar collagens I and II, the two most predominant types. By comparing X-ray diffraction data collected from type I and type II containing tissues, we point to evidence for a range of triple-helical symmetries being extant in the molecules native environment. The possible significance of helical instability, local helix dissociation and molecular packing of the triple-helices is discussed in the context of collagen's supramolecular organization, all of which must affect the symmetry of the collagen triple-helix.

  17. Structure/Function Analysis of Cotton-Based Peptide-Cellulose Conjugates: Spatiotemporal/Kinetic Assessment of Protease Aerogels Compared to Nanocrystalline and Paper Cellulose

    Directory of Open Access Journals (Sweden)

    J. Vincent Edwards

    2018-03-01

    Full Text Available Nanocellulose has high specific surface area, hydration properties, and ease of derivatization to prepare protease sensors. A Human Neutrophil Elastase sensor designed with a nanocellulose aerogel transducer surface derived from cotton is compared with cotton filter paper, and nanocrystalline cellulose versions of the sensor. X-ray crystallography was employed along with Michaelis–Menten enzyme kinetics, and circular dichroism to contrast the structure/function relations of the peptide-cellulose conjugate conformation to enzyme/substrate binding and turnover rates. The nanocellulosic aerogel was found to have a cellulose II structure. The spatiotemporal relation of crystallite surface to peptide-cellulose conformation is discussed in light of observed enzyme kinetics. A higher substrate binding affinity (Km of elastase was observed with the nanocellulose aerogel and nanocrystalline peptide-cellulose conjugates than with the solution-based elastase substrate. An increased Km observed for the nanocellulosic aerogel sensor yields a higher enzyme efficiency (kcat/Km, attributable to binding of the serine protease to the negatively charged cellulose surface. The effect of crystallite size and β-turn peptide conformation are related to the peptide-cellulose kinetics. Models demonstrating the orientation of cellulose to peptide O6-hydroxymethyl rotamers of the conjugates at the surface of the cellulose crystal suggest the relative accessibility of the peptide-cellulose conjugates for enzyme active site binding.

  18. Structure/Function Analysis of Cotton-Based Peptide-Cellulose Conjugates: Spatiotemporal/Kinetic Assessment of Protease Aerogels Compared to Nanocrystalline and Paper Cellulose

    Science.gov (United States)

    Edwards, J. Vincent; Fontenot, Krystal; Liebner, Falk; Pircher, Nicole Doyle nee; French, Alfred D.; Condon, Brian D.

    2018-01-01

    Nanocellulose has high specific surface area, hydration properties, and ease of derivatization to prepare protease sensors. A Human Neutrophil Elastase sensor designed with a nanocellulose aerogel transducer surface derived from cotton is compared with cotton filter paper, and nanocrystalline cellulose versions of the sensor. X-ray crystallography was employed along with Michaelis–Menten enzyme kinetics, and circular dichroism to contrast the structure/function relations of the peptide-cellulose conjugate conformation to enzyme/substrate binding and turnover rates. The nanocellulosic aerogel was found to have a cellulose II structure. The spatiotemporal relation of crystallite surface to peptide-cellulose conformation is discussed in light of observed enzyme kinetics. A higher substrate binding affinity (Km) of elastase was observed with the nanocellulose aerogel and nanocrystalline peptide-cellulose conjugates than with the solution-based elastase substrate. An increased Km observed for the nanocellulosic aerogel sensor yields a higher enzyme efficiency (kcat/Km), attributable to binding of the serine protease to the negatively charged cellulose surface. The effect of crystallite size and β-turn peptide conformation are related to the peptide-cellulose kinetics. Models demonstrating the orientation of cellulose to peptide O6-hydroxymethyl rotamers of the conjugates at the surface of the cellulose crystal suggest the relative accessibility of the peptide-cellulose conjugates for enzyme active site binding. PMID:29534033

  19. Molecular dynamics investigation of the influence of anionic and zwitterionic interfaces on antimicrobial peptides' structure: implications for peptide toxicity and activity

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N

    2006-01-01

    Molecular dynamics simulations of three related helical antimicrobial peptides have been carried out in zwitterionic diphosphocholine (DPC) micelles and anionic sodiumdodecylsulfate (SDS) micelles. These systems can be considered as model mammalian and bacterial membrane interfaces, respectively...

  20. Protein 3D structure computed from evolutionary sequence variation.

    Directory of Open Access Journals (Sweden)

    Debora S Marks

    Full Text Available The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing.In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy.We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues, including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7-4.8 Å C(α-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org. This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of

  1. Variation of backscatter as an indicator of boundary layer structure

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, M. [UMIST, Dept. of Chemical Engineering, Manchester (United Kingdom); Hunter, G.C. [National Power, Swindon (United Kingdom)

    1997-10-01

    In this work we have developed software to display cross-sections of the variance of backscatter over a given sampling period in addition to its absolute mean. We have analyzed a series of Lidar cross-sections of elevated plumes dispersing into a convective BL and have then derived profiles both of the mean backscatter, , as a function of height and of its relative, shot-to-shot, variation, {radical} /. The latter is a measure of the homogeneity of the aerosol. There is no cheap device for measuring BL depths so we were interested in comparing depths estimated using our Lidar with those predicted by the current ADMS atmospheric dispersion model. This is based on integrating an energy budget to predict the BL development and as such relies on values for the initial lapse rate and for the surface sensible heat flux. A major shortcoming of the model appears to be that, in the absence of measurements, it must assume a default value for the former; the latter may be estimated from surface measurements but is very sensitive to the assumed availability of surface moisture. (LN)

  2. Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain.

    Science.gov (United States)

    Laskowski, Roman A; Tyagi, Nidhi; Johnson, Diana; Joss, Shelagh; Kinning, Esther; McWilliam, Catherine; Splitt, Miranda; Thornton, Janet M; Firth, Helen V; Wright, Caroline F

    2016-03-01

    We present a generic, multidisciplinary approach for improving our understanding of novel missense variants in recently discovered disease genes exhibiting genetic heterogeneity, by combining clinical and population genetics with protein structural analysis. Using six new de novo missense diagnoses in TBL1XR1 from the Deciphering Developmental Disorders study, together with population variation data, we show that the β-propeller structure of the ubiquitous WD40 domain provides a convincing way to discriminate between pathogenic and benign variation. Children with likely pathogenic mutations in this gene have severely delayed language development, often accompanied by intellectual disability, autism, dysmorphology and gastrointestinal problems. Amino acids affected by likely pathogenic missense mutations are either crucial for the stability of the fold, forming part of a highly conserved symmetrically repeating hydrogen-bonded tetrad, or located at the top face of the β-propeller, where 'hotspot' residues affect the binding of β-catenin to the TBLR1 protein. In contrast, those altered by population variation are significantly less likely to be spatially clustered towards the top face or to be at buried or highly conserved residues. This result is useful not only for interpreting benign and pathogenic missense variants in this gene, but also in other WD40 domains, many of which are associated with disease. © The Author 2016. Published by Oxford University Press.

  3. A conformal gauge invariant functional for Weyl structures and the first variation formula

    OpenAIRE

    Ichiyama, Toshiyuki; Furuhata, Hitoshi; Urakawa, Hajime

    1999-01-01

    We consider a new conformal gauge invariant functional which is a natural curvature functional on the space of Weyl structures. We derive the first variation formula of its functional and characterize its critical points.

  4. Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome

    NARCIS (Netherlands)

    Collins, Ryan L; Brand, Harrison; Redin, Claire E.; Hanscom, Carrie; Antolik, Caroline; Stone, Matthew R; Glessner, Joseph T.; Mason, Tamara; Pregno, Giulia; Dorrani, Naghmeh; Mandrile, Giorgia; Giachino, Daniela; Perrin, Danielle; Walsh, Cole; Cipicchio, Michelle; Costello, Maura; Stortchevoi, Alexei; An, Joon Yong; Currall, Benjamin B; Seabra, Catarina M; Ragavendran, Ashok; Margolin, Lauren; Martinez-Agosto, Julian A.; Lucente, Diane; Levy, Brynn; Sanders, Jan-Stephan; Wapner, Ronald J.; Quintero-Rivera, Fabiola; Kloosterman, Wigard; Talkowski, Michael E.

    2017-01-01

    Background: Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. Results: We sequenced 689 participants with autism spectrum disorder (ASD) and other

  5. Genetic Variation in Schizophrenia Liability is Shared With Intellectual Ability and Brain Structure

    NARCIS (Netherlands)

    Bohlken, Marc M; Brouwer, Rachel M; Mandl, René C W; Kahn, René S; Hulshoff Pol, Hilleke E

    2016-01-01

    BACKGROUND: Alterations in intellectual ability and brain structure are important genetic markers for schizophrenia liability. How variations in these phenotypes interact with variance in schizophrenia liability due to genetic or environmental factors is an area of active investigation. Studying

  6. Variation in the Helical Structure of Native Collagen

    Science.gov (United States)

    2014-02-24

    notochord were obtained in previous studies [4,10,20–22]. The scaled amplitudes of the central, meridional section of each data set were used to...including helical, structure) from rat tail tendon (collagen type I) and lamprey notochord (collagen type II) show several common features (Figure 5). Of...also a possible consequence of the type II collagen notochord samples being stretched, perhaps to a greater extant then the type I tendon samples to aid

  7. Transferrin variation and genetic structure of reindeer populations in Scandinavia

    Directory of Open Access Journals (Sweden)

    Knut H. Røed

    1987-06-01

    Full Text Available Polyacrylamide gel electrophoresis was used to analyse transferrin variation in herds of semi-domestic reindeer from Scandinavia. The results are compared with previously reported values for other populations of both semi-domestic and wild reindeer using the same techniques as in the present study. In all populations the number of alleles was high, ranging from seven to eleven, and the heterozygosity was correspondingly high, with a mean of 0.749. This high genetic variation in all populations suggests that inbreeding is not widespread among Scandinavian reindeer. The pattern of allele frequency distribution indicates a high degree of genetic heterogeneity in the transferrin locus, both between the different semi-domestic herds and between the different wild populations. The mean value of genetic distance was 0.069 between semi-domestic herds and 0.091 between wild populations. Between semi-domestic and wild populations the genetic distance was particularly high, with a mean of 0.188. This high value was mainly due to a different pattern in the distribution of the two most common transferrin alleles: Tfu was most common among semi-domestic herds, while TfEI was most common among wild populations. These differences in transferrin allele distribution are discussed in relation to possible different origins of semi-domestic and wild reindeer in Scandinavia, or alternatively, to different selection forces acting on transferrin genotypes in semi-domestic and wild populations.Transferrin-variasjon og genetisk struktur hos rein i Skandinavia.Abstact in Norwegian / Sammendrag: Transferrin-variasjon i tamreinflokker ble analysert ved hjelp av polyacrylamid gel elektroforese. Resultatene er sammenlignet med verdier som tidligere er beskrevet for både tamrein og villrein hvor det ble benyttet samme metode som i denne undersøkelsen. I alle populasjonene ble det registrert et høyt antall alleler (7-11 og heterozygositeten var tilsvarende høy med en

  8. Sensitivity of ultracold-atom scattering experiments to variation of the fine-structure constant

    International Nuclear Information System (INIS)

    Borschevsky, A.; Beloy, K.; Flambaum, V. V.; Schwerdtfeger, P.

    2011-01-01

    We present numerical calculations for cesium and mercury to estimate the sensitivity of the scattering length to the variation of the fine-structure constant α. The method used follows the ideas of Chin and Flambaum [Phys. Rev. Lett. 96, 230801 (2006)], where the sensitivity to the variation of the electron-to-proton mass ratio β was considered. We demonstrate that for heavy systems, the sensitivity to the variation of α is of the same order of magnitude as to the variation of β. Near narrow Feshbach resonances, the enhancement of the sensitivity may exceed nine orders of magnitude.

  9. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  10. Differential CLE peptide perception by plant receptors implicated from structural and functional analyses of TDIF-TDR interactions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou; Kobe, Bostjan

    2017-04-06

    Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells. Here we present the crystal structures of the extracellular domains (ECD) of TDR alone and in complex with its ligand TDIF resolved at 2.65 Åand 2.75 Å respectively. These structures provide insights about the ligand perception and specific interactions between the CLE peptides and their cognate receptors. Our in vitro biochemical studies indicate that the interactions between the ligands and the receptors at the C-terminal anchoring site provide conserved binding. While the binding interactions occurring at the N-terminal anchoring site dictate differential binding specificities between different ligands and receptors. Our studies will open different unknown avenues of TDR-TDIF signaling pathways that will enhance our knowledge in this field highlighting the receptor ligand interaction, receptor activation, signaling network, modes of action and will serve as a structure function relationship model between the ligand and the receptor for various similar leucine-rich repeat receptor-like kinases (LRR-RLKs).

  11. Variation in the crustal structure across central Iceland

    Science.gov (United States)

    Du, Zhijun; Foulger, G. R.

    2001-04-01

    We determine the crustal structures beneath 12 broad-band seismic stations deployed in a swath across central Iceland along and around the ICEMELT explosion seismic profile by combining teleseismic receiver functions, surface wave dispersion curves and the waveforms of a large, local event in Iceland. By using teleseisms that approach from different backazimuths, we study lateral structural variability out of the line of the ICEMELT profile. Beneath Tertiary areas, the thickness of the upper crust, as defined by the 6.5kms-1 velocity horizon, is ~8km and the depth to the base of the lower crust, as defined by the 7.2kms-1 velocity horizon, is ~29-32km. Beneath the currently active rift zone the upper crust thins to ~6.0km and the depth to the base of the lower crust increases to ~35-40km. A substantial low-velocity zone underlies the Middle Volcanic Zone in the lower crust, which may indicate anomalously high geothermal gradients there. This suggests that the large-scale thermal centre of the hotspot may be more westerly than northwest Vatnajokull, where it is generally assumed to lie. Simplified description of the results notwithstanding, there is substantial variability in the overall style of crustal structure throughout Iceland, and a clear, tripartite division into upper and lower crusts and a sharp Moho is poorly supported by many of our results. The nature, distinctiveness and continuity of the Moho is variable and in many areas the crust-mantle transition is a zone with enhanced velocity gradients several kilometres thick.

  12. Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation

    Directory of Open Access Journals (Sweden)

    Pero Stephanie C

    2007-09-01

    Full Text Available Abstract Background Human growth factor receptor bound protein 7 (Grb7 is an adapter protein that mediates the coupling of tyrosine kinases with their downstream signaling pathways. Grb7 is frequently overexpressed in invasive and metastatic human cancers and is implicated in cancer progression via its interaction with the ErbB2 receptor and focal adhesion kinase (FAK that play critical roles in cell proliferation and migration. It is thus a prime target for the development of novel anti-cancer therapies. Recently, an inhibitory peptide (G7-18NATE has been developed which binds specifically to the Grb7 SH2 domain and is able to attenuate cancer cell proliferation and migration in various cancer cell lines. Results As a first step towards understanding how Grb7 may be inhibited by G7-18NATE, we solved the crystal structure of the Grb7 SH2 domain to 2.1 Å resolution. We describe the details of the peptide binding site underlying target specificity, as well as the dimer interface of Grb 7 SH2. Dimer formation of Grb7 was determined to be in the μM range using analytical ultracentrifugation for both full-length Grb7 and the SH2 domain alone, suggesting the SH2 domain forms the basis of a physiological dimer. ITC measurements of the interaction of the G7-18NATE peptide with the Grb7 SH2 domain revealed that it binds with a binding affinity of Kd = ~35.7 μM and NMR spectroscopy titration experiments revealed that peptide binding causes perturbations to both the ligand binding surface of the Grb7 SH2 domain as well as to the dimer interface, suggesting that dimerisation of Grb7 is impacted on by peptide binding. Conclusion Together the data allow us to propose a model of the Grb7 SH2 domain/G7-18NATE interaction and to rationalize the basis for the observed binding specificity and affinity. We propose that the current study will assist with the development of second generation Grb7 SH2 domain inhibitors, potentially leading to novel inhibitors of

  13. Structure of the Paramyxovirus Parainfluenza Virus 5 Nucleoprotein in Complex with an Amino-Terminal Peptide of the Phosphoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Aggarwal, Megha; Leser, George P.; Kors, Christopher A.; Lamb, Robert A.; Sundquist, Wesley I.

    2017-12-13

    Parainfluenza virus 5 (PIV5) belongs to the familyParamyxoviridae, which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (N0P) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 N0P consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNA-bound PIV5 N was previously shown to be an RNA binding site. The N0P structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication.

    IMPORTANCEParamyxovirus replication is regulated by the interaction of P with N and L proteins. Here, we report the crystal structure of unassembled parainfluenza virus 5 (PIV5) N chaperoned with P peptide. Our results provide a detailed understanding of the binding of P to N. The conformational switching of N between closed and open forms during its initial interaction with P, as well as

  14. A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere.

    Science.gov (United States)

    Rutenber, E E; McPhee, F; Kaplan, A P; Gallion, S L; Hogan, J C; Craik, C S; Stroud, R M

    1996-09-01

    The essential role of HIV-1 protease (HIV-1 PR) in the viral life cycle makes it an attractive target for the development of substrate-based inhibitors that may find efficacy as anti-AIDS drugs. However, resistance has arisen to potent peptidomimetic drugs necessitating the further development of novel chemical backbones for diversity based chemistry focused on probing the active site for inhibitor interactions and binding modes that evade protease resistance. AQ148 is a potent inhibitor of HIV-1 PR and represents a new class of transition state analogues incorporating an aminimide peptide isostere. A 3-D crystallographic structure of AQ148, a tetrapeptide isostere, has been determined in complex with its target HIV-1 PR to a resolution of 2.5 A and used to evaluate the specific structural determinants of AQ148 potency and to correlate structure-activity relationships within the class of related compounds. AQ148 is a competitive inhibitor of HIV-1 PR with a Ki value of 137 nM. Twenty-nine derivatives have been synthesized and chemical modifications have been made at the P1, P2, P1', and P2' sites. The atomic resolution structure of AQ148 bound to HIV-1 PR reveals both an inhibitor binding mode that closely resembles that of other peptidomimetic inhibitors and specific protein/inhibitor interactions that correlate with structure-activity relationships. The structure provides the basis for the design, synthesis and evaluation of the next generation of hydroxyethyl aminimide inhibitors. The aminimide peptide isostere is a scaffold with favorable biological properties well suited to both the combinatorial methods of peptidomimesis and the rational design of potent and specific substrate-based analogues.

  15. Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis.

    Science.gov (United States)

    Hsu, Cheng-Lung; Liu, Jai-Shin; Wu, Po-Long; Guan, Hong-Hsiang; Chen, Yuh-Ling; Lin, An-Chi; Ting, Huei-Ju; Pang, See-Tong; Yeh, Shauh-Der; Ma, Wen-Lung; Chen, Chung-Jung; Wu, Wen-Guey; Chang, Chawnshang

    2014-12-01

    Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. Variations in Velopharyngeal Structure in Adults With Repaired Cleft Palate.

    Science.gov (United States)

    Perry, Jamie L; Kotlarek, Katelyn J; Sutton, Bradley P; Kuehn, David P; Jaskolka, Michael S; Fang, Xiangming; Point, Stuart W; Rauccio, Frank

    2018-01-01

    The purpose of this study was to examine differences in velopharyngeal structures between adults with repaired cleft palate and normal resonance and adults without cleft palate. Thirty-six English-speaking adults, including 6 adults (2 males and 4 females) with repaired cleft palate (M = 32.5 years of age, SD = 17.4 years) and 30 adults (15 males and 15 females) without cleft palate (M = 23.3 years of age, SD = 4.1 years), participated in the study. Fourteen velopharyngeal measures were obtained on magnetic resonance images and compared between groups (cleft and noncleft). After adjusting for body size and sex effects, there was a statistically significant difference between groups for 10 out of the 14 velopharyngeal measures. Compared to those without cleft palate, participants with repaired cleft palate had a significantly shorter hard palate height and length, shorter levator muscle length, shorter intravelar segment, more acute levator angles of origin, shorter and thinner velum, and greater pharyngeal depth. Although significant differences were evident in the cleft palate group, individuals displayed normal resonance. These findings suggest that a wide variability in velopharyngeal anatomy can occur in the presence of normal resonance, particularly for those with repaired cleft palate. Future research is needed to understand how anatomic variability impacts function, such as during speech.

  17. Spatial variation of phytoplankton community structure in Daya Bay, China.

    Science.gov (United States)

    Jiang, Zhao-Yu; Wang, You-Shao; Cheng, Hao; Zhang, Jian-Dong; Fei, Jiao

    2015-10-01

    Daya Bay is one of the largest and most important gulfs in the southern coast of China, in the northern part of the South China Sea. The phylogenetic diversity and spatial distribution of phytoplankton from the Daya Bay surface water and the relationship with the in situ water environment were investigated by the clone library of the large subunit of ribulose-1, 5-bisphosphate carboxylase (rbcL) gene. The dominant species of phytoplankton were diatoms and eustigmatophytes, which accounted for 81.9 % of all the clones of the rbcL genes. Prymnesiophytes were widely spread and wide varieties lived in Daya Bay, whereas the quantity was limited. The community structure of phytoplankton was shaped by pH and salinity and the concentration of silicate, phosphorus and nitrite. The phytoplankton biomass was significantly positively affected by phosphorus and nitrite but negatively by salinity and pH. Therefore, the phytoplankton distribution and biomass from Daya Bay were doubly affected by anthropic activities and natural factors.

  18. Structural Variations to a Donor Polymer with Low Energy Losses

    KAUST Repository

    Bazan, Guillermo C

    2017-08-01

    Two regioregular narrow band gap conjugated polymers with a D’-A-D-A repeat unit architecture, namely PIFCF and PSFCF, were designed and synthesized. Both polymers contain strictly organized fluorobenzo[c][1,2,5]thiadiazole (FBT) orientations and different solubilizing side chains for solution processing. Compared to the previously reported asymmetric pyridyl-[2,1,3]thiadiazole (PT) based regioregular polymer, namely PIPCP, PIFCF and PSFCF exhibit wider band gaps, tighter π-π stacking, and improved hole mobilities. When incorporated into solar cells with fullerene acceptors, the Eloss = Eg - eVoc values of PIFCF and PSFCF devices are increased compared to solar cells based on PIPCP. Determination of Ect in these solar cells reveals that, relative to PIPCP, PIFCF solar cells lose more energy from Eg - Ect, and PSFCF solar cells lose more energy from both Eg - Ect and Ect - eVoc. The close structural relationship between PIPCP and PIFCF provides an excellent framework to establish molecular features that impact the relationship between Eg and Ect. Theoretical calculations predict that Eloss of PIFCF:PC61BM would be higher than in the case of PIPCP:PC61BM, due to greater Eg - Ect. These findings provide insight into the design of high performance, low voltage loss photovoltaic polymeric materials with desirable optoelectronic properties.

  19. Structural and functional characterization of human apolipoprotein E 72-166 peptides in both aqueous and lipid environments

    Directory of Open Access Journals (Sweden)

    Chou Chi-Yuan

    2011-01-01

    Full Text Available Abstract Backgrounds There are three apolipoprotein E (apoE isoforms involved in human lipid homeostasis. In the present study, truncated apoE2-, apoE3- and apoE4-(72-166 peptides that are tailored to lack domain interactions are expressed and elucidated the structural and functional consequences. Methods & Results Circular dichroism analyses indicated that their secondary structure is still well organized. Analytical ultracentrifugation analyses demonstrated that apoE-(72-166 produces more complicated species in PBS. All three isoforms were significantly dissociated in the presence of dihexanoylphosphatidylcholine. Dimyristoylphosphatidylcholine turbidity clearance assay showed that apoE4-(72-166 maintains the highest lipid-binding capacity. Finally, only apoE4-(72-166 still maintained significant LDL receptor binding ability. Conclusions Overall, apoE4-(72-166 peptides displayed a higher lipid-binding and comparable receptor-binding ability as to full-length apoE. These findings provide the explanation of diverged functionality of truncated apoE isoforms.

  20. Variation of structural damping with response amplitude in piping systems

    International Nuclear Information System (INIS)

    Ware, A.G.

    1986-01-01

    From tests conducted over the last several years, it has become apparent that structural damping is not a single number applicable to all piping systems, but is highly dependent on piping system parameters such as supports, response amplitude, and insulation. As a result, there is considerable scatter in the available data. Furthermore, the relationships between the parameters and damping are often highly complex, interrelated, and difficult to predict. From tests of piping supported by various typical methods, two basic types of energy dissipation in the supports can be observed. The first is friction such as between spring hangers and their housings or in the internal mechanisms of constant force hangers. The second is impacting such as occurs in snubbers, rigid struts, and rod hangers. Overall, these effects lead to a wide variety of possibilities that can occur at low vibration levels and can change with only a slight perturbation of vibration amplitude. This can account for much of the scatter in the data at low strain levels. Thus damping is almost impossible to predict at low amplitudes, and extrapolation of this type data to higher amplitudes is cautioned. However, once strain levels rise above 100 to 200 micro in/in, the damping trend becomes easier to characterize. From the 100 to 200 micro in/in to 800 to 1000 micro in/in range the damping is fairly constant and is induced primarily by the supports. At the upper end of this range a threshold is reached in which damping increases with increasing strain amplitude. Data in the high strain (plastic range) is sparse since the test usually renders the pipe unsuitable for further use. 15 refs

  1. Structure-Related Roles for the Conservation of the HIV-1 Fusion Peptide Sequence Revealed by Nuclear Magnetic Resonance.

    Science.gov (United States)

    Serrano, Soraya; Huarte, Nerea; Rujas, Edurne; Andreu, David; Nieva, José L; Jiménez, María Angeles

    2017-10-17

    Despite extensive characterization of the human immunodeficiency virus type 1 (HIV-1) hydrophobic fusion peptide (FP), the structure-function relationships underlying its extraordinary degree of conservation remain poorly understood. Specifically, the fact that the tandem repeat of the FLGFLG tripeptide is absolutely conserved suggests that high hydrophobicity may not suffice to unleash FP function. Here, we have compared the nuclear magnetic resonance (NMR) structures adopted in nonpolar media by two FP surrogates, wtFP-tag and scrFP-tag, which had equal hydrophobicity but contained wild-type and scrambled core sequences LFLGFLG and FGLLGFL, respectively. In addition, these peptides were tagged at their C-termini with an epitope sequence that folded independently, thereby allowing Western blot detection without interfering with FP structure. We observed similar α-helical FP conformations for both specimens dissolved in the low-polarity medium 25% (v/v) 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), but important differences in contact with micelles of the membrane mimetic dodecylphosphocholine (DPC). Thus, whereas wtFP-tag preserved a helix displaying a Gly-rich ridge, the scrambled sequence lost in great part the helical structure upon being solubilized in DPC. Western blot analyses further revealed the capacity of wtFP-tag to assemble trimers in membranes, whereas membrane oligomers were not observed in the case of the scrFP-tag sequence. We conclude that, beyond hydrophobicity, preserving sequence order is an important feature for defining the secondary structures and oligomeric states adopted by the HIV FP in membranes.

  2. The assembly and properties of protobiological structures - The beginnings of cellular peptide synthesis

    Science.gov (United States)

    Fox, S. W.; Nakashima, T.

    1980-01-01

    New data indicate that lysine-rich proteinoids have the ability to catalyze the synthesis of peptide bonds from a variety of amino acids and ATP. This capacity is evident in aqueous solution, in suspension of phase-separated complexes of lysine-rich proteinoid with acidic proteinoids, and in suspension of phase-separated particles composed of lysine-rich proteinoids with polynucleotides. Since the proteinoid complexes can contain other catalytic activities, including ability to catalyze internucleotide bond formation, it is inferred that the first protocells on earth already had a number of biological types of activity.

  3. Identification of genomic indels and structural variations using split reads

    Directory of Open Access Journals (Sweden)

    Urban Alexander E

    2011-07-01

    Full Text Available Abstract Background Recent studies have demonstrated the genetic significance of insertions, deletions, and other more complex structural variants (SVs in the human population. With the development of the next-generation sequencing technologies, high-throughput surveys of SVs on the whole-genome level have become possible. Here we present split-read identification, calibrated (SRiC, a sequence-based method for SV detection. Results We start by mapping each read to the reference genome in standard fashion using gapped alignment. Then to identify SVs, we score each of the many initial mappings with an assessment strategy designed to take into account both sequencing and alignment errors (e.g. scoring more highly events gapped in the center of a read. All current SV calling methods have multilevel biases in their identifications due to both experimental and computational limitations (e.g. calling more deletions than insertions. A key aspect of our approach is that we calibrate all our calls against synthetic data sets generated from simulations of high-throughput sequencing (with realistic error models. This allows us to calculate sensitivity and the positive predictive value under different parameter-value scenarios and for different classes of events (e.g. long deletions vs. short insertions. We run our calculations on representative data from the 1000 Genomes Project. Coupling the observed numbers of events on chromosome 1 with the calibrations gleaned from the simulations (for different length events allows us to construct a relatively unbiased estimate for the total number of SVs in the human genome across a wide range of length scales. We estimate in particular that an individual genome contains ~670,000 indels/SVs. Conclusions Compared with the existing read-depth and read-pair approaches for SV identification, our method can pinpoint the exact breakpoints of SV events, reveal the actual sequence content of insertions, and cover the whole

  4. Temporal variation in bat-fruit interactions: Foraging strategies influence network structure over time

    Science.gov (United States)

    Zapata-Mesa, Natalya; Montoya-Bustamante, Sebastián; Murillo-García, Oscar E.

    2017-11-01

    Mutualistic interactions, such as seed dispersal, are important for the maintenance of structure and stability of tropical communities. However, there is a lack of information about spatial and temporal variation in plant-animal interaction networks. Thus, our goal was to assess the effect of bat's foraging strategies on temporal variation in the structure and robustness of bat-fruit networks in both a dry and a rain tropical forest. We evaluated monthly variation in bat-fruit networks by using seven structure metrics: network size, average path length, nestedness, modularity, complementary specialization, normalized degree and betweenness centrality. Seed dispersal networks showed variations in size, species composition and modularity; did not present nested structures and their complementary specialization was high compared to other studies. Both networks presented short path lengths, and a constantly high robustness, despite their monthly variations. Sedentary bat species were recorded during all the study periods and occupied more central positions than nomadic species. We conclude that foraging strategies are important structuring factors that affect the dynamic of networks by determining the functional roles of frugivorous bats over time; thus sedentary bats are more important than nomadic species for the maintenance of the network structure, and their conservation is a must.

  5. Structural characterization of peptides derived from prosomatostatins I and II isolated from the pancreatic islets of two species of teleostean fish: the daddy sculpin and the flounder.

    Science.gov (United States)

    Conlon, J M; Davis, M S; Falkmer, S; Thim, L

    1987-11-02

    The primary structures of three peptides from extracts from the pancreatic islets of the daddy sculpin (Cottus scorpius) and three analogous peptides from the islets of the flounder (Platichthys flesus), two species of teleostean fish, have been determined by automated Edman degradation. The structures of the flounder peptides were confirmed by fast-atom bombardment mass spectrometry. The peptides show strong homology to residues (49-60), (63-96) and (98-125) of the predicted sequence of preprosomatostatin II from the anglerfish (Lophius americanus). The amino acid sequences of the peptides suggest that, in the sculpin, prosomatostatin II is cleaved at a dibasic amino acid residue processing site (corresponding to Lys61-Arg62 in anglerfish preprosomatostatin II). The resulting fragments are further cleaved at monobasic residue processing sites (corresponding to Arg48 and Arg97 in anglerfish preprosomatostatin II). In the flounder the same dibasic residue processing site is utilised but cleavage at different monobasic sites takes place (corresponding to Arg50 and Arg97 in anglerfish preprosomatostatin II). A peptide identical to mammalian somatostatin-14 was also isolated from the islets of both species and is presumed to represent a cleavage product of prosomatostatin I.

  6. Structural variations in aromatic 2π-electron three-membered rings ...

    Indian Academy of Sciences (India)

    Abstract. Structural variations of different 2π-aromatic three-membered ring systems of main group ele- ments, especially group 14 and 13 elements as compared to the classical description of cyclopropenyl cation has been reviewed in this article. The structures of heavier analogues as well as group 13 analogues of cyclo-.

  7. Towards Structural Analysis of Audio Recordings in the Presence of Musical Variations

    Directory of Open Access Journals (Sweden)

    Müller Meinard

    2007-01-01

    Full Text Available One major goal of structural analysis of an audio recording is to automatically extract the repetitive structure or, more generally, the musical form of the underlying piece of music. Recent approaches to this problem work well for music, where the repetitions largely agree with respect to instrumentation and tempo, as is typically the case for popular music. For other classes of music such as Western classical music, however, musically similar audio segments may exhibit significant variations in parameters such as dynamics, timbre, execution of note groups, modulation, articulation, and tempo progression. In this paper, we propose a robust and efficient algorithm for audio structure analysis, which allows to identify musically similar segments even in the presence of large variations in these parameters. To account for such variations, our main idea is to incorporate invariance at various levels simultaneously: we design a new type of statistical features to absorb microvariations, introduce an enhanced local distance measure to account for local variations, and describe a new strategy for structure extraction that can cope with the global variations. Our experimental results with classical and popular music show that our algorithm performs successfully even in the presence of significant musical variations.

  8. The preparation, cytocompatibility and antimicrobial property of micro/nano structural titanium loading alginate and antimicrobial peptide

    Science.gov (United States)

    Liu, Zhiyuan; Zhong, Mou; Sun, Yuhua; Chen, Junhong; Feng, Bo

    2018-03-01

    Titanium with hybrid microporous/nanotubes (TMNT) structure on its surface was fabricated by acid etching and subsequently anodization at different voltages. Bovine lactoferricin, a kind of antimicrobial peptide, and sodium alginate (NaAlg) were loaded onto titanium surface through layer by layer assembly. The drug release, cytocompatibility and antimicrobial property against S.aureus and E.coil were studied by release experiment, osteoblast and bacterial cultures. Results indicated that samples with nanotubes of bigger diameter carried more drugs and had better biocompatibility, and drug-loaded samples acquired better biocompatibility compared with drug-free samples. Furthermore, the drug-loaded samples exhibited good initial antimicrobial property, but weak long-term antimicrobial property. Therefore, drug-loaded titanium with micro/nano structure, especially, of big diameter nanotubes, could be a promise material for medical implants, such as internal/external fixation devices.

  9. Structure characterization of the central repetitive domain of high molecular weight gluten proteins .1. Model studies using cyclic and linear peptides

    NARCIS (Netherlands)

    VanDijk, AA; VanWijk, LL; VanVliet, A; Haris, P; VanSwieten, E; Tesser, GI; Robillard, GT

    The high molecular weight (HMW) proteins from wheat contain a repetitive domain that forms 60-80% of their sequence. The consensus peptides PGQGQQ and GYYPTSPQQ form more than 90% of the domain; both are predicted to adopt beta-turn structure. This paper describes the structural characterization of

  10. Rational design of DKK3 structure-based small peptides as antagonists of Wnt signaling pathway and in silico evaluation of their efficiency.

    Directory of Open Access Journals (Sweden)

    Mansour Poorebrahim

    Full Text Available Dysregulated Wnt signaling pathway is highly associated with the pathogenesis of several human cancers. Dickkopf proteins (DKKs are thought to inhibit Wnt signaling pathway through binding to lipoprotein receptor-related protein (LRP 5/6. In this study, based on the 3-dimensional (3D structure of DKK3 Cys-rich domain 2 (CRD2, we have designed and developed several peptide inhibitors of Wnt signaling pathway. Modeller 9.15 package was used to predict 3D structure of CRD2 based on the Homology modeling (HM protocol. After refinement and minimization with GalaxyRefine and NOMAD-REF servers, the quality of selected models was evaluated utilizing VADAR, SAVES and ProSA servers. Molecular docking studies as well as literature-based information revealed two distinct boxes located at CRD2 which are actively involved in the DKK3-LRP5/6 interaction. A peptide library was constructed conducting the backrub sequence tolerance scanning protocol in Rosetta3.5 according to the DKK3-LRP5/6 binding sites. Seven tolerated peptides were chosen and their binding affinity and stability were improved by some logical amino acid substitutions. Molecular dynamics (MD simulations of peptide-LRP5/6 complexes were carried out using GROMACS package. After evaluation of binding free energies, stability, electrostatic potential and some physicochemical properties utilizing computational approaches, three peptides (PEP-I1, PEP-I3 and PEP-II2 demonstrated desirable features. However, all seven improved peptides could sufficiently block the Wnt-binding site of LRP6 in silico. In conclusion, we have designed and improved several small peptides based on the LRP6-binding site of CRD2 of DKK3. These peptides are highly capable of binding to LRP6 in silico, and may prevent the formation of active Wnt-LRP6-Fz complex.

  11. Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function

    KAUST Repository

    Rydberg, Hanna A.; Carlsson, Nils; Nordé n, Bengt

    2012-01-01

    of arg/trp peptides and investigated how the position and number of tryptophans affect cellular uptake. Here we explore the antimicrobial properties and the interaction with lipid model membranes of these peptides, using minimal inhibitory concentrations

  12. Molecular descriptor subset selection in theoretical peptide quantitative structure-retention relationship model development using nature-inspired optimization algorithms.

    Science.gov (United States)

    Žuvela, Petar; Liu, J Jay; Macur, Katarzyna; Bączek, Tomasz

    2015-10-06

    In this work, performance of five nature-inspired optimization algorithms, genetic algorithm (GA), particle swarm optimization (PSO), artificial bee colony (ABC), firefly algorithm (FA), and flower pollination algorithm (FPA), was compared in molecular descriptor selection for development of quantitative structure-retention relationship (QSRR) models for 83 peptides that originate from eight model proteins. The matrix with 423 descriptors was used as input, and QSRR models based on selected descriptors were built using partial least squares (PLS), whereas root mean square error of prediction (RMSEP) was used as a fitness function for their selection. Three performance criteria, prediction accuracy, computational cost, and the number of selected descriptors, were used to evaluate the developed QSRR models. The results show that all five variable selection methods outperform interval PLS (iPLS), sparse PLS (sPLS), and the full PLS model, whereas GA is superior because of its lowest computational cost and higher accuracy (RMSEP of 5.534%) with a smaller number of variables (nine descriptors). The GA-QSRR model was validated initially through Y-randomization. In addition, it was successfully validated with an external testing set out of 102 peptides originating from Bacillus subtilis proteomes (RMSEP of 22.030%). Its applicability domain was defined, from which it was evident that the developed GA-QSRR exhibited strong robustness. All the sources of the model's error were identified, thus allowing for further application of the developed methodology in proteomics.

  13. Precise colocalization of interacting structural and pigmentary elements generates extensive color pattern variation in Phelsuma lizards

    Science.gov (United States)

    2013-01-01

    Background Color traits in animals play crucial roles in thermoregulation, photoprotection, camouflage, and visual communication, and are amenable to objective quantification and modeling. However, the extensive variation in non-melanic pigments and structural colors in squamate reptiles has been largely disregarded. Here, we used an integrated approach to investigate the morphological basis and physical mechanisms generating variation in color traits in tropical day geckos of the genus Phelsuma. Results Combining histology, optics, mass spectrometry, and UV and Raman spectroscopy, we found that the extensive variation in color patterns within and among Phelsuma species is generated by complex interactions between, on the one hand, chromatophores containing yellow/red pteridine pigments and, on the other hand, iridophores producing structural color by constructive interference of light with guanine nanocrystals. More specifically, we show that 1) the hue of the vivid dorsolateral skin is modulated both by variation in geometry of structural, highly ordered narrowband reflectors, and by the presence of yellow pigments, and 2) that the reflectivity of the white belly and of dorsolateral pigmentary red marks, is increased by underlying structural disorganized broadband reflectors. Most importantly, these interactions require precise colocalization of yellow and red chromatophores with different types of iridophores, characterized by ordered and disordered nanocrystals, respectively. We validated these results through numerical simulations combining pigmentary components with a multilayer interferential optical model. Finally, we show that melanophores form dark lateral patterns but do not significantly contribute to variation in blue/green or red coloration, and that changes in the pH or redox state of pigments provide yet another source of color variation in squamates. Conclusions Precisely colocalized interacting pigmentary and structural elements generate extensive

  14. Adamantoylated biologically active small peptides and glycopeptides structurally related to the bacterial peptidoglycan.

    Science.gov (United States)

    Frkanec, Ruža; Vranešić, Branka; Tomić, Srdjanka

    2013-01-01

    A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity, particularly immunomodulating properties. A series of compounds containing the adamantyl residues coupled to peptides and glycopeptides characteristic for bacterial peptidoglycan was described. The new adamantylpeptides and adamantylglycopeptides were prepared starting from N-protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the starting material was D,L-(adamantyl-glycine) the condensation products with the dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were separated, characterized, and tested for immunostimulating activity. An HPLC method for purity testing was developed and adapted for the particular compounds.

  15. Pyridyl-alanine as a Hydrophilic, Aromatic Element in Peptide Structural Optimization.

    Science.gov (United States)

    Mroz, Piotr A; Perez-Tilve, Diego; Liu, Fa; Gelfanov, Vasily; DiMarchi, Richard D; Mayer, John P

    2016-09-08

    Glucagon (Gcg) 1 serves a seminal physiological role in buffering against hypoglycemia, but its poor biophysical properties severely complicate its medicinal use. We report a series of novel glucagon analogues of enhanced aqueous solubility and stability at neutral pH, anchored by Gcg[Aib16]. Incorporation of 3- and 4-pyridyl-alanine (3-Pal and 4-Pal) enhanced aqueous solubility of glucagon while maintaining biological properties. Relative to native hormone, analogue 9 (Gcg[3-Pal6,10,13, Aib16]) demonstrated superior biophysical character, better suitability for medicinal purposes, and comparable pharmacology against insulin-induced hypoglycemia in rats and pigs. Our data indicate that Pal is a versatile surrogate to natural aromatic amino acids and can be employed as an alternative or supplement with isoelectric adjustment to refine the biophysical character of peptide drug candidates.

  16. Determining suitable lego-structures to estimate stability of larger peptide nanostructures using computational methods.

    Science.gov (United States)

    Beke, Tamás; Czajlik, András; Csizmadia, Imre G; Perczel, András

    2006-02-02

    Nanofibers, nanofilms and nanotubes constructed of one to four strands of oligo-alpha- and oligo-beta-peptides were obtained by using carefully selected building units. Lego-type approaches based on thermoneutral isodesmic reactions can be used to reconstruct the total energies of both linear and tubular periodic nanostructures with acceptable accuracy. Total energies of several different nanostructures were accurately determined with errors typically falling in the subchemical range. Thus, attention will be focused on the description of suitable isodesmic reactions that have enabled the determination of the total energy of polypeptides and therefore offer a very fast, efficient and accurate method to obtain energetic information on large and even very large nanosystems.

  17. Stereochemical Basis for a Unified Structure Activity Theory of Aromatic and Heterocyclic Rings in Selected Opioids and Opioid Peptides

    Directory of Open Access Journals (Sweden)

    Joel S. Goldberg

    2010-02-01

    Full Text Available This paper presents a novel unified theory of the structure activity relationship of opioids and opioid peptides. It is hypothesized that a virtual or known heterocyclic ring exists in all opioids which have activity in humans, and this ring occupies relative to the aromatic ring of the drug, approximately the same plane in space as the piperidine ring of morphine. Since the rings of morphine are rigid, and the aromatic and piperidine rings are critical structural components for morphine’s analgesic properties, the rigid morphine molecule allows for approximations of the aromatic and heterocyclic relationships in subsequent drug models where bond rotations are common. This hypothesis and five propositions are supported by stereochemistry and experimental observations. Proposition #1 The structure of morphine provides a template. Proposition #2 Steric hindrance of some centric portion of the piperidine ring explains antagonist properties of naloxone, naltrexone and alvimopam. Proposition #3 Methadone has an active conformation which contains a virtual heterocyclic ring which explains its analgesic activity and racemic properties. Proposition #4 The piperidine ring of fentanyl can assume the morphine position under conditions of nitrogen inversion. Proposition #5 The first 3 amino acid sequences of beta endorphin (l-try-gly-gly and the active opioid dipeptide, l-tyr-pro, (as a result of a peptide turn and zwitterion bonding form a virtual piperazine-like ring which is similar in size, shape and location to the heterocyclic rings of morphine, meperidine, and methadone. Potential flaws in this theory are discussed. This theory could be important for future analgesic drug design.

  18. The effect of a beta-lactamase inhibitor peptide on bacterial membrane structure and integrity: a comparative study.

    Science.gov (United States)

    Alaybeyoglu, Begum; Uluocak, Bilge Gedik; Akbulut, Berna Sariyar; Ozkirimli, Elif

    2017-05-01

    Co-administration of beta-lactam antibiotics and beta-lactamase inhibitors has been a favored treatment strategy against beta-lactamase-mediated bacterial antibiotic resistance, but the emergence of beta-lactamases resistant to current inhibitors necessitates the discovery of novel non-beta-lactam inhibitors. Peptides derived from the Ala46-Tyr51 region of the beta-lactamase inhibitor protein are considered as potent inhibitors of beta-lactamase; unfortunately, peptide delivery into the cell limits their potential. The properties of cell-penetrating peptides could guide the design of beta-lactamase inhibitory peptides. Here, our goal is to modify the peptide with the sequence RRGHYY that possesses beta-lactamase inhibitory activity under in vitro conditions. Inspired by the work on the cell-penetrating peptide pVEC, our approach involved the addition of the N-terminal hydrophobic residues, LLIIL, from pVEC to the inhibitor peptide to build a chimera. These residues have been reported to be critical in the uptake of pVEC. We tested the potential of RRGHYY and its chimeric derivative as a beta-lactamase inhibitory peptide on Escherichia coli cells and compared the results with the action of the antimicrobial peptide melittin, the beta-lactam antibiotic ampicillin, and the beta-lactamase inhibitor potassium clavulanate to get mechanistic details on their action. Our results show that the addition of LLIIL to the N-terminus of the beta-lactamase inhibitory peptide RRGHYY increases its membrane permeabilizing potential. Interestingly, the addition of this short stretch of hydrophobic residues also modified the inhibitory peptide such that it acquired antimicrobial property. We propose that addition of the hydrophobic LLIIL residues to the peptide N-terminus offers a promising strategy to design novel antimicrobial peptides in the battle against antibiotic resistance. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European

  19. High performance liquid chromatography (HPLC fingerprints and primary structure identification of corn peptides by HPLC-diode array detection and HPLC-electrospray ionization tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Chi Wang

    2016-01-01

    Full Text Available Corn peptides (CPs are reported to have many biological functions, such as facilitating alcohol metabolism, antioxidation, antitumor, antihypertension, and hepatoprotection. To develop a method for quality control, the high-performance liquid chromatography (HPLC system was applied. Twenty-eight common peaks were found in all the CPs of corn samples from Enshi, China, based on which, a fingerprinting chromatogram was established for use in quality control in future research. Subsequently, the major chemical constituents of these common peaks were identified respectively using the HPLC-diode-array detection electrospray ionization tandem mass spectrometry (DAD-ESI-MS/MS system, and 48 peptide fractions were determined ultimately. This was the first time for the majority of these peptides to be reported, and many of them contained amino acids of glutamine (Q, L and A, which might play an important role in the exhibition of the bioactivities of CPs. Many peptides had a similar primary structure to the peptides which had been proven to be bioactive such as facilitating alcohol metabolism, scavenging free radicals, and inhibiting lipid peroxidation. This systematical analysis of the primary structure of CPs facilitated subsequent studies on the relationship between the structures and functions, and could accelerate holistic research on CPs.

  20. Structure-activity relationship study of Aib-containing amphipathic helical peptide-cyclic RGD conjugates as carriers for siRNA delivery.

    Science.gov (United States)

    Wada, Shun-Ichi; Takesada, Anna; Nagamura, Yurie; Sogabe, Eri; Ohki, Rieko; Hayashi, Junsuke; Urata, Hidehito

    2017-12-15

    The conjugation of Aib-containing amphipathic helical peptide with cyclo(-Arg-Gly-Asp-d-Phe-Cys-) (cRGDfC) at the C-terminus of the helix peptide (PI) has been reported to be useful for constructing a carrier for targeted siRNA delivery into cells. In order to explore structure-activity relationships for the development of potential carriers for siRNA delivery, we synthesized conjugates of Aib-containing amphipathic helical peptide with cRGDfC at the N-terminus (PII) and both the N- and C-termini (PIII) of the helical peptide. Furthermore, to examine the influence of PI helical chain length on siRNA delivery, truncated peptides containing 16 (PIV), 12 (PV), and 8 (PVI) amino acid residues at the N-terminus of the helical chain were synthesized. PII and PIII, as well as PI, could deliver anti-luciferase siRNA into cells to induce the knockdown of luciferase stably expressed in cells. In contrast, all of the truncated peptides were unlikely to transport siRNA into cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.

    Directory of Open Access Journals (Sweden)

    Victoria S Paulsen

    Full Text Available Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2 terminus of the peptide and the fragment arasin 1(1-23 was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23 were shown to be non-toxic to human red blood cells and arasin 1(1-23 was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23 was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC, arasin 1(1-23 was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23 has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23 involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.

  2. Production of recombinant disulfide-rich venom peptides for structural and functional analysis via expression in the periplasm of E. coli.

    Directory of Open Access Journals (Sweden)

    Julie K Klint

    Full Text Available Disulfide-rich peptides are the dominant component of most animal venoms. These peptides have received much attention as leads for the development of novel therapeutic agents and bioinsecticides because they target a wide range of neuronal receptors and ion channels with a high degree of potency and selectivity. In addition, their rigid disulfide framework makes them particularly well suited for addressing the crucial issue of in vivo stability. Structural and functional characterization of these peptides necessitates the development of a robust, reliable expression system that maintains their native disulfide framework. The bacterium Escherichia coli has long been used for economical production of recombinant proteins. However, the expression of functional disulfide-rich proteins in the reducing environment of the E. coli cytoplasm presents a significant challenge. Thus, we present here an optimised protocol for the expression of disulfide-rich venom peptides in the periplasm of E. coli, which is where the endogenous machinery for production of disulfide-bonds is located. The parameters that have been investigated include choice of media, induction conditions, lysis methods, methods of fusion protein and peptide purification, and sample preparation for NMR studies. After each section a recommendation is made for conditions to use. We demonstrate the use of this method for the production of venom peptides ranging in size from 2 to 8 kDa and containing 2-6 disulfide bonds.

  3. Landscape and variation of RNA secondary structure across the human transcriptome.

    Science.gov (United States)

    Wan, Yue; Qu, Kun; Zhang, Qiangfeng Cliff; Flynn, Ryan A; Manor, Ohad; Ouyang, Zhengqing; Zhang, Jiajing; Spitale, Robert C; Snyder, Michael P; Segal, Eran; Chang, Howard Y

    2014-01-30

    In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.

  4. Cosmological constraints on variations of the fine structure constant at the epoch of recombination

    International Nuclear Information System (INIS)

    Menegoni, E; Galli, S; Archidiacono, M; Calabrese, E; Melchiorri, A

    2013-01-01

    In this brief work we investigate any possible variation of the fine structure constant at the epoch of recombination. The recent measurements of the Cosmic Microwave Background anisotropies at arcminute angular scales performed by the ACT and SPT experiments are probing the damping regime of Cosmic Microwave Background fluctuations. We study the role of a mechanism that could affect the shape of the Cosmic Microwave Background angular fluctuations at those scales, namely a change in the recombination process through variations in the fine structure constant α

  5. Disulfide-stabilized Helical Hairpin Structure and Activity of a Novel Antifungal Peptide EcAMP1 from Seeds of Barnyard Grass (Echinochloa crus-galli)*

    Science.gov (United States)

    Nolde, Svetlana B.; Vassilevski, Alexander A.; Rogozhin, Eugene A.; Barinov, Nikolay A.; Balashova, Tamara A.; Samsonova, Olga V.; Baranov, Yuri V.; Feofanov, Alexey V.; Egorov, Tsezi A.; Arseniev, Alexander S.; Grishin, Eugene V.

    2011-01-01

    This study presents purification, activity characterization, and 1H NMR study of the novel antifungal peptide EcAMP1 from kernels of barnyard grass Echinochloa crus-galli. The peptide adopts a disulfide-stabilized α-helical hairpin structure in aqueous solution and thus represents a novel fold among naturally occurring antimicrobial peptides. Micromolar concentrations of EcAMP1 were shown to inhibit growth of several fungal phytopathogens. Confocal microscopy revealed intensive EcAMP1 binding to the surface of fungal conidia followed by internalization and accumulation in the cytoplasm without disturbance of membrane integrity. Close spatial structure similarity between EcAMP1, the trypsin inhibitor VhTI from seeds of Veronica hederifolia, and some scorpion and cone snail toxins suggests natural elaboration of different functions on a common fold. PMID:21561864

  6. Disulfide-stabilized helical hairpin structure and activity of a novel antifungal peptide EcAMP1 from seeds of barnyard grass (Echinochloa crus-galli).

    Science.gov (United States)

    Nolde, Svetlana B; Vassilevski, Alexander A; Rogozhin, Eugene A; Barinov, Nikolay A; Balashova, Tamara A; Samsonova, Olga V; Baranov, Yuri V; Feofanov, Alexey V; Egorov, Tsezi A; Arseniev, Alexander S; Grishin, Eugene V

    2011-07-15

    This study presents purification, activity characterization, and (1)H NMR study of the novel antifungal peptide EcAMP1 from kernels of barnyard grass Echinochloa crus-galli. The peptide adopts a disulfide-stabilized α-helical hairpin structure in aqueous solution and thus represents a novel fold among naturally occurring antimicrobial peptides. Micromolar concentrations of EcAMP1 were shown to inhibit growth of several fungal phytopathogens. Confocal microscopy revealed intensive EcAMP1 binding to the surface of fungal conidia followed by internalization and accumulation in the cytoplasm without disturbance of membrane integrity. Close spatial structure similarity between EcAMP1, the trypsin inhibitor VhTI from seeds of Veronica hederifolia, and some scorpion and cone snail toxins suggests natural elaboration of different functions on a common fold.

  7. Mining the protein data bank to differentiate error from structural variation in clustered static structures: an examination of HIV protease.

    Science.gov (United States)

    Venkatakrishnan, Balasubramanian; Palii, Miorel-Lucian; Agbandje-McKenna, Mavis; McKenna, Robert

    2012-03-01

    The Protein Data Bank (PDB) contains over 71,000 structures. Extensively studied proteins have hundreds of submissions available, including mutations, different complexes, and space groups, allowing for application of data-mining algorithms to analyze an array of static structures and gain insight about a protein's structural variation and possibly its dynamics. This investigation is a case study of HIV protease (PR) using in-house algorithms for data mining and structure superposition through generalized formulæ that account for multiple conformations and fractional occupancies. Temperature factors (B-factors) are compared with spatial displacement from the mean structure over the entire study set and separately over bound and ligand-free structures, to assess the significance of structural deviation in a statistical context. Space group differences are also examined.

  8. Fusing simulation and experiment: The effect of mutations on the structure and activity of the influenza fusion peptide

    Science.gov (United States)

    Lousa, Diana; Pinto, Antónia R. T.; Victor, Bruno L.; Laio, Alessandro; Veiga, Ana S.; Castanho, Miguel A. R. B.; Soares, Cláudio M.

    2016-01-01

    During the infection process, the influenza fusion peptide (FP) inserts into the host membrane, playing a crucial role in the fusion process between the viral and host membranes. In this work we used a combination of simulation and experimental techniques to analyse the molecular details of this process, which are largely unknown. Although the FP structure has been obtained by NMR in detergent micelles, there is no atomic structure information in membranes. To answer this question, we performed bias-exchange metadynamics (BE-META) simulations, which showed that the lowest energy states of the membrane-inserted FP correspond to helical-hairpin conformations similar to that observed in micelles. BE-META simulations of the G1V, W14A, G12A/G13A and G4A/G8A/G16A/G20A mutants revealed that all the mutations affect the peptide’s free energy landscape. A FRET-based analysis showed that all the mutants had a reduced fusogenic activity relative to the WT, in particular the mutants G12A/G13A and G4A/G8A/G16A/G20A. According to our results, one of the major causes of the lower activity of these mutants is their lower membrane affinity, which results in a lower concentration of peptide in the bilayer. These findings contribute to a better understanding of the influenza fusion process and open new routes for future studies. PMID:27302370

  9. Effect of pulsed electric field (PEF) on structures and antioxidant activity of soybean source peptides-SHCMN.

    Science.gov (United States)

    Lin, Songyi; Liang, Rong; Li, Xingfang; Xing, Jie; Yuan, Yuan

    2016-12-15

    Recently, high-intensity pulsed electric field (PEF) has successfully used in improvement of antioxidant activity. Ser-His-Cys-Met-Asn (SHCMN) obtained from soybean protein was chosen to investigate the phenomenon of antioxidant activity improvement. Effects of PEF treatment on antioxidant activity of SHCMN were evaluated by DPPH radical inhibition. Nuclear magnetic resonance (NMR), mid-infrared (MIR), circular dichroism (CD) were used to analyze structures of SHCMN. Two-factor-at-a-time results show that DPPH radical inhibition of SHCMN is significantly (Pfield intensity of 5kV/cm, pulse frequency of 2400Hz, and retention time of 2h. In addition, MIR and NMR spectra show that the basic structure of peptides SHCMN is stable by PEF treatment. But the secondary structures (α-helix, β-turn, and random coil) can be affected and zeta potential of PEF-treated SHCNM was reduced to 0.59±0.03mV. The antioxidant activity improvement of SHCMN might result from the changes of secondary structures and zeta potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. On the Environmental Factors Affecting the Structural and Cytotoxic Properties of IAPP Peptides

    Directory of Open Access Journals (Sweden)

    Marianna Flora Tomasello

    2015-01-01

    Full Text Available Pancreatic islets in type 2 diabetes mellitus (T2DM patients are characterized by reduced β-cells mass and diffuse extracellular amyloidosis. Amyloid deposition involves the islet amyloid polypeptide (IAPP, a neuropancreatic hormone cosecreted with insulin by β-cells. IAPP is physiologically involved in glucose homeostasis, but it may turn toxic to β-cells owing to its tendency to misfold giving rise to oligomers and fibrils. The process by which the unfolded IAPP starts to self-assemble and the overall factors promoting this conversion are poorly understood. Other open questions are related to the nature of the IAPP toxic species and how exactly β-cells die. Over the last decades, there has been growing consensus about the notion that early molecular assemblies, notably small hIAPP oligomers, are the culprit of β-cells decline. Numerous environmental factors might affect the conformational, aggregation, and cytotoxic properties of IAPP. Herein we review recent progress in the field, focusing on the influences that membranes, pH, and metal ions may have on the conformational conversion and cytotoxicity of full-length IAPP as well as peptide fragments thereof. Current theories proposed for the mechanisms of toxicity will be also summarized together with an outline of the underlying molecular links between IAPP and amyloid beta (Aβ misfolding.

  11. Solution structure of the 45-residue ATP-binding peptide of adenylate kinase as determined by 2-D NMR, FTIR, and CD spectroscopy

    International Nuclear Information System (INIS)

    Fry, D.C.; Byler, D.M.; Susi, H.; Brown, E.M.; Kuby, S.A.; Mildyan, A.S.

    1986-01-01

    In the X-ray structure of adenylate kinase residues 1-45 exist as 47% α-helix, 29% β-structure (strands and turns) and 24% coil. The solution structure of a synthetic peptide corresponding to residues 1-45, which constitutes the MgATP binding site was studied by 3 independent spectroscopic methods. Globularity of the peptide was shown by its broad NMR resonances which narrow upon denaturation, and by its ability to bind MgATP with similar affinity and conformation as the intact enzyme does. COSY and NOESY NMR methods at 250 and 500 MHz reveal proximities among NH, Cα, and Cβ protons indicative of >20% α-helix, and >20% β-structure. Correlation of regions of secondary structure with the primary sequence by 2D NMR indicates at least one α-helix (res. 23 to 29) and two β-strands (res. 12 to 15 and 34 to 38). The broad amide I band in the deconvoluted FTIR spectrum could be fit as the sum of 4 peaks due to specific secondary structures, yielding ≤=45% α-helix, ≤=40% β-structure and ≥=15% coil. The CD spectrum, from 185-250 nm, interpreted with a 3-parameter basis set, yielded 20 +/- 5% α=helix, and ≤=20% β-structure. The solution structure of peptide 1-45 thus approximates that of residues 1-45 in the crystal

  12. Structural and functional comparisons and production of recombinant crustacean hyperglycemic hormone (CHH) and CHH-like peptides from the mud crab Scylla olivacea.

    Science.gov (United States)

    Chang, Chih-Chun; Tsai, Kuo-Wei; Hsiao, Nai-Wan; Chang, Cheng-Yen; Lin, Chih-Lung; Watson, R Douglas; Lee, Chi-Ying

    2010-05-15

    Sco-CHH and Sco-CHH-L (CHH-like peptide), two structural variants of the crustacean hyperglycemic hormone family identified in the mud crab (Scylla olivacea), are presumably alternatively spliced gene products. In this study, Sco-CHH and Sco-CHH-L were isolated from the tissues using high performance liquid chromatography. Identity of the native peptides was confirmed using mass spectrometric (MS) analyses of purified materials and of trypsin-digested peptide fragments. Additionally, characterizations using circular dichroism (CD) spectrometry revealed that the 2 peptides have similar CD spectral profiles, showing they are composed mainly of alpha-helices, and are similarly thermo-stable with a melting temperature of 74-75 degrees C. Results of bioassays indicated that Sco-CHH exerted hyperglycemic and molt-inhibiting activity, whereas Sco-CHH-L did not. Further, recombinant Sco-CHH-Gly (rSco-CHH-Gly, a glycine extended Sco-CHH) and Sco-CHH-L (rSco-CHH-L) were produced using an Escherichia coli expression system, refolded, and purified. rSco-CHH-Gly was further alpha-amidated at the C-terminal end to produce rSco-CHH. MS analyses of enzyme-digested peptide fragments of rSco-CHH-Gly and rSco-CHH-L showed that the two peptides share a common disulfide bond pattern: C7-C43, C23-C39, and C26-C52. Circular dichroism analyses and hyperglycemic assay revealed that rSco-CHH and rSco-CHH-L resemble their native counterparts, in terms of CD spectral profiles, melting curve profiles, and biological activity. rSco-CHH-Gly has a lower alpha-helical content (32%) than rSco-CHH (47%), a structural deviation that may be responsible for the significant decrease in the biological activity of rSco-CHH-Gly. Finally, modeled structure of Sco-CHH and Sco-CHH-L indicated that they are similarly folded, each with an N-terminal tail region and 4 alpha-helices. Putative surface residues located in corresponding positions of Sco-CHH and Sco-CHH-L but with side chains of different properties

  13. Climatic factors, genetic structure and phenotypic variation in English yew (Taxus baccata L.)

    OpenAIRE

    Mayol, Maria; Berganzo, Elisa; Burgarella, Concetta; González-Martínez, Santiago C.; Grivet, Delphine; Vendramin, Giovanni G.; Vincenot, Lucie; Riba, Miquel

    2018-01-01

    Influence of climatic factors on genetic structure and phenotypic variation in English yew (Taxus baccata L.) Conference "Adapting to global change in the Mediterranean hotspot" (Seville, 18-20 September 2013) Mediterranean forests constitute long-term reservoirs of biodiversity and adaptive potential. As compared with their central or northern European counterparts, Mediterranean forests are characterized by highly heterogeneous and fragmented environments, ...

  14. The determination of the in situ structure by nuclear spin contrast variation

    Energy Technology Data Exchange (ETDEWEB)

    Stuhrmann, H.B. [GKSS Forschungszentrum, Geesthacht (Germany); Nierhaus, K.H. [Max-Planch-Institut fuer Molekulare Genetik, Berlin (Germany)

    1994-12-31

    Polarized neutron scattering from polarized nuclear spins in hydrogenous substances opens a new way of contrast variation. The enhanced contrast due to proton spin polarization was used for the in situ structure determination of tRNA of the functional complex of the E.coli ribosome.

  15. Variation in xylem structure from tropics to tundra: Evidence from vestured pits

    NARCIS (Netherlands)

    Jansen, S.; Baas, P.; Gasson, P.; Lens, F.; Smets, E.

    2004-01-01

    Bordered pits play an important role in permitting water flow among adjacent tracheary elements in flowering plants. Variation in the bordered pit structure is suggested to be adaptive in optimally balancing the conflict between hydraulic efficiency (conductivity) and safety from air entry at the

  16. Phosphorylation Variation during the Cell Cycle Scales with Structural Propensities of Proteins

    DEFF Research Database (Denmark)

    Tyanova, S.; Frishman, D.; Cox, J.

    2013-01-01

    of the cell division cycle we investigate how the variation of the amount of phosphorylation correlates with the protein structure in the vicinity of the modified site. We find two distinct phosphorylation site groups: intrinsically disordered regions tend to contain sites with dynamically varying levels...

  17. SV-AUTOPILOT: optimized, automated construction of structural variation discovery and benchmarking pipelines

    NARCIS (Netherlands)

    W.Y. Leung; T. Marschall (Tobias); Y. Paudel; L. Falquet; H. Mei (Hailiang); A. Schönhuth (Alexander); T.Y. Maoz

    2015-01-01

    htmlabstractBackground Many tools exist to predict structural variants (SVs), utilizing a variety of algorithms. However, they have largely been developed and tested on human germline or somatic (e.g. cancer) variation. It seems appropriate to exploit this wealth of technology available for humans

  18. The determination of the in situ structure by nuclear spin contrast variation

    International Nuclear Information System (INIS)

    Stuhrmann, H.B.; Nierhaus, K.H.

    1994-01-01

    Polarized neutron scattering from polarized nuclear spins in hydrogenous substances opens a new way of contrast variation. The enhanced contrast due to proton spin polarization was used for the in situ structure determination of tRNA of the functional complex of the E.coli ribosome

  19. Variation in mangrove forest structure and sediment characteristics in Bocas del Toro, Panama

    Science.gov (United States)

    Lovelock, C.E.; Feller, Ilka C.; McKee, K.L.; Thompson, R.

    2005-01-01

    Mangrove forest structure and sediment characteristics were examined in the extensive mangroves of Bocas del Toro, Republic of Panama. Forest structure was characterized to determine if spatial vegetation patterns were repeated over the Bocas del Toro landscape. Using a series of permanent plots and transects we found that the forests of Bocas del Toro were dominated by Rhizophora mangle with very few individuals of Avicennia germinans and Laguncularia racemosa. Despite this low species diversity, there was large variation in forest structure and in edaphic conditions (salinity, concentration of available phosphorus, Eh and sulphide concentration). Aboveground biomass varied 20-fold, from 6.8 Mg ha-1 in dwarf forests to 194.3 Mg ha-1 in the forests fringing the land. But variation in forest structure was predictable across the intertidal zone. There was a strong tree height gradient from seaward fringe (mean tree height 3.9 m), decreasing in stature in the interior dwarf forests (mean tree height 0.7 m), and increasing in stature in forests adjacent to the terrestrial forest (mean tree height 4.1 m). The predictable variation in forest structure emerges due to the complex interactions among edaphic and plant factors. Identifying predictable patterns in forest structure will aid in scaling up the ecosystem services provided by mangrove forests in coastal landscapes. Copyright 2005 College of Arts and Sciences.

  20. [Plant signaling peptides. Cysteine-rich peptides].

    Science.gov (United States)

    Ostrowski, Maciej; Kowalczyk, Stanisław

    2015-01-01

    Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation.

  1. A synthetic peptide derived from the animo acid sequence of canine parvovirus structural proteins which defines a B cell epitope and elicits antiviral antibody in BALB c mice.

    NARCIS (Netherlands)

    G.F. Rimmelzwaan (Guus); J. Carlson; F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1990-01-01

    textabstractSynthetic peptides, recombinant fusion proteins and mouse monoclonal antibodies were used to delineate a B cell epitope of the VP'2 structural protein of canine parvovirus (CPV). Although this epitope is not preferentially recognized in the normal antibody response to CPV, virus-specific

  2. Room-temperature synthesis of core-shell structured magnetic covalent organic frameworks for efficient enrichment of peptides and simultaneous exclusion of proteins.

    Science.gov (United States)

    Lin, Guo; Gao, Chaohong; Zheng, Qiong; Lei, Zhixian; Geng, Huijuan; Lin, Zian; Yang, Huanghao; Cai, Zongwei

    2017-03-28

    Core-shell structured magnetic covalent organic frameworks (Fe 3 O 4 @COFs) were synthesized via a facile approach at room temperature. Combining the advantages of high porosity, magnetic responsiveness, chemical stability and selectivity, Fe 3 O 4 @COFs can serve as an ideal absorbent for the highly efficient enrichment of peptides and the simultaneous exclusion of proteins from complex biological samples.

  3. Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization

    Czech Academy of Sciences Publication Activity Database

    Pepin, R.; Laszlo, K. J.; Marek, Aleš; Peng, B.; Bush, M. F.; Lavanant, H.; Afonso, C.; Tureček, F.

    2016-01-01

    Roč. 27, č. 10 (2016), s. 1647-1660 ISSN 1044-0305 Institutional support: RVO:61388963 Keywords : peptide ions * ion mobility * collisional cross sections * density functional theory calculations * ion structures * polar effects Subject RIV: CC - Organic Chemistry Impact factor: 2.786, year: 2016

  4. Structural characterization of the interactions between calmodulin and skeletal muscle myosin light chain kinase: Effect of peptide (576-594)G binding on the Ca2+-binding domains

    International Nuclear Information System (INIS)

    Seeholzer, S.H.; Wand, A.J.

    1989-01-01

    Calcium-containing calmodulin (CaM) and its complex with a peptide corresponding to the calmodulin-binding domain of skeletal muscle myosin light chain kinase [skMLCK(576-594)G] have been studied by one- and two-dimensional 1 H NMR techniques. Resonances arising from the antiparallel β-sheet structures associated with the calcium-binding domains of CaM and their counterparts in the CaM-skMLCK(576-594)G complex have been assigned. The assignments were initiated by application of the main chain directed assignment strategy. It is found that, despite significant changes in chemical shifts of resonances arising from amino acid residues in this region upon binding of the peptide, the β-sheets have virtually the same structure in the complex as in CaM. Hydrogen exchange rates of amide NH within the β-sheet structures are significantly slowed upon binding of peptide. These data, in conjunction with the observed nuclear Overhauser effect (NOE) patterns and relative intensities and the downfield shifts of associated amide and α resonances upon binding of peptide, show that the peptide stabilizes the Ca 2+ -bound state of calmodulin. The observed pattern of NOEs within the β-sheets and their structural similarity correspond closely to those predicted by the crystal structure. These findings imply that the apparent inconsistency of the crystal structure with recently reported low-angle X-ray scattering profiles of CaM may lie within the putative central helix bridging the globular domains

  5. Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis

    International Nuclear Information System (INIS)

    McMahon, Róisín M.; Friis, Lone; Siebold, Christian; Friese, Manuel A.; Fugger, Lars; Jones, E. Yvonne

    2011-01-01

    The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. HLA-A3 is a predisposing allele for multiple sclerosis (MS), an autoimmune disease of the central nervous system. The KLIETYFSK peptide is a naturally processed epitope of proteolipid protein, a myelin protein and candidate target for immune-mediated myelin destruction in MS. Comparison of the structure of HLA-A3 with that of HLA-A2, an MHC class I molecule which is protective against MS, indicates that both MHC class I molecules present very similar faces for T-cell receptor recognition whilst differing in the specificity of their peptide-binding grooves. These characteristics may underlie the opposing (predisposing versus protective) associations that they exhibit both in humans and in mouse models of MS-like disease. Furthermore, subtle alterations within the peptide-binding groove of HLA-A3 and other A3-like MHC class I molecules, members of the so-called A3 superfamily, may be sufficient to alter their presentation of autoantigen peptides such as KLIETYFSK. This in turn may modulate their contribution to the associated risk of autoimmune disease

  6. Changes in the structure of calmodulin induced by a peptide based on the calmodulin-binding domain of myosin light chain kinase

    International Nuclear Information System (INIS)

    Heidorn, D.B.; Seeger, P.A.; Rokop, S.E.; Blumenthal, D.K.; Means, A.R.; Crespi, H.; Trewhella, J.

    1989-01-01

    Small-angle X-ray and neutron scattering data were used to study the solution structure of calmodulin complexed with a synthetic peptide corresponding to residues 577-603 of rabbit skeletal muscle myosin light chain kinase. The X-ray data indicate that, in the presence of Ca 2+ , the calmodulin-peptide complex has a structure that is considerably more compact than uncomplexed calmodulin. The radius of gyration, R g , for the complex is approximately 20% smaller than that of uncomplexed Ca 2+ ·calmodulin, and the maximum dimension, d max , for the complex is also about 20% smaller. The peptide-induced conformational rearrangement of calmodulin is [Ca 2+ ] dependent. The length distribution function for the complex is more symmetric than that for uncomplexed Ca 2+ ·calmodulin, indicating that more of the mass is distributed toward the center of mass for the complex, compared with the dumbbell-shaped Ca 2+ ·calmodulin. The solvent contrast dependence of R g for neutron scattering indicates that the peptide is located more toward the center of the complex, while the calmodulin is located more peripherally, and that the centers of mass of the calmodulin and the peptide are not coincident. The scattering data support the hypothesis that the interconnecting helix region observed in the crystal structure for calmodulin is quite flexible in solution, allowing the two lobes of calmodulin to form close contacts on binding the peptide. This flexibility of the central helix may play a critical role in activating target enzymes such as myosin light chain kinase

  7. Structure and function of the first full-length murein peptide ligase (Mpl cell wall recycling protein.

    Directory of Open Access Journals (Sweden)

    Debanu Das

    2011-03-01

    Full Text Available Bacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-diaminopimelyl-D-alanyl-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc. MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In gram-negative bacteria, ∼30-60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl, which attaches the breakdown product, the tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 Å resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl. Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters. Although the structure does not contain any bound substrates, we have identified ∼30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships.

  8. Structure and function of the first full-length murein peptide ligase (Mpl) cell wall recycling protein.

    Science.gov (United States)

    Das, Debanu; Hervé, Mireille; Feuerhelm, Julie; Farr, Carol L; Chiu, Hsiu-Ju; Elsliger, Marc-André; Knuth, Mark W; Klock, Heath E; Miller, Mitchell D; Godzik, Adam; Lesley, Scott A; Deacon, Ashley M; Mengin-Lecreulx, Dominique; Wilson, Ian A

    2011-03-18

    Bacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-γ-D-glutamyl-meso-diaminopimelyl-D-alanyl-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc). MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In gram-negative bacteria, ∼30-60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl), which attaches the breakdown product, the tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 Å resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl). Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters). Although the structure does not contain any bound substrates, we have identified ∼30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships.

  9. Primary and secondary structure dependence of peptide flexibility assessed by fluorescence-based measurement of end-to-end collision rates.

    Science.gov (United States)

    Huang, Fang; Hudgins, Robert R; Nau, Werner M

    2004-12-22

    The intrachain fluorescence quenching of the fluorophore 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) is measured in short peptide fragments, namely the two strands and the turn of the N-terminal beta-hairpin of ubiquitin. The investigated peptides adopt a random-coil conformation in aqueous solution according to CD and NMR experiments. The combination of quenchers with different quenching efficiencies, namely tryptophan and tyrosine, allows the extrapolation of the rate constants for end-to-end collision rates as well as the dissociation of the end-to-end encounter complex. The measured activation energies for fluorescence quenching demonstrate that the end-to-end collision process in peptides is partially controlled by internal friction within the backbone, while measurements in solvents of different viscosities (H2O, D2O, and 7.0 M guanidinium chloride) suggest that solvent friction is an additional important factor in determining the collision rate. The extrapolated end-to-end collision rates, which are only slightly larger than the experimental rates for the DBO/Trp probe/quencher system, provide a measure of the conformational flexibility of the peptide backbone. The chain flexibility is found to be strongly dependent on the type of secondary structure that the peptides represent. The collision rates for peptides derived from the beta-strand motifs (ca. 1 x 10(7) s(-1)) are ca. 4 times slower than that derived from the beta-turn. The results provide further support for the hypothesis that chain flexibility is an important factor in the preorganization of protein fragments during protein folding. Mutations to the beta-turn peptide show that subtle sequence changes strongly affect the flexibility of peptides as well. The protonation and charge status of the peptides, however, are shown to have no significant effect on the flexibility of the investigated peptides. The meaning and definition of end-to-end collision rates in the context of protein folding are critically

  10. Dissecting the Structure-Function Relationship of a Fungicidal Peptide Derived from the Constant Region of Human Immunoglobulins

    OpenAIRE

    Ciociola, Tecla; Pertinhez, Thelma A.; Giovati, Laura; Sperindè, Martina; Magliani, Walter; Ferrari, Elena; Gatti, Rita; D'Adda, Tiziana; Spisni, Alberto; Conti, Stefania; Polonelli, Luciano

    2016-01-01

    Synthetic peptides encompassing sequences related to the complementarity-determining regions of antibodies or derived from their constant region (Fc peptides) were proven to exert differential antimicrobial, antiviral, antitumor, and/or immunomodulatory activities in vitro and/or in vivo, regardless of the specificity and isotype of the parental antibody. Alanine substitution derivatives of these peptides exhibited unaltered, increased, or decreased candidacidal activities in vitro. The bioac...

  11. Connective tissue activation. XXXII. Structural and biologic characteristics of mesenchymal cell-derived connective tissue activating peptide-V.

    Science.gov (United States)

    Cabral, A R; Cole, L A; Walz, D A; Castor, C W

    1987-12-01

    Connective tissue activating peptide-V (CTAP-V) is a single-chain, mesenchymal cell-derived anionic protein with large and small molecular forms (Mr of 28,000 and 16,000, respectively), as defined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins have similar specific activities with respect to stimulation of hyaluronic acid and DNA formation in human synovial fibroblast cultures. S-carboxymethylation or removal of sialic acid residues did not modify CTAP-V biologic activity. Rabbit antibodies raised separately against each of the purified CTAP-V proteins reacted, on immunodiffusion and on Western blot, with each antigen and neutralized mitogenic activity. The amino-terminal amino acid sequence of the CTAP-V proteins, determined by 2 laboratories, confirmed their structural similarities. The amino-terminal sequence through 37 residues was demonstrated for the smaller protein. The first 10 residues of CTAP-V (28 kd) were identical to the N-terminal decapeptide of CTAP-V (16 kd). The C-terminal sequence, determined by carboxypeptidase Y digestion, was the same for both CTAP-V molecular species. The 2 CTAP-V peptides had similar amino acid compositions, whether residues were expressed as a percent of the total or were normalized to mannose. Reduction of native CTAP-V protein released sulfhydryl groups in a protein:disulfide ratio of 1:2; this suggests that CTAP-V contains 2 intramolecular disulfide bonds. Clearly, CTAP-V is a glycoprotein. The carbohydrate content of CTAP-V (16 kd) and CTAP-V (28 kd) is 27% and 25%, respectively. CTAP-V may have significance in relation to autocrine mechanisms for growth regulation of connective tissue cells and other cell types.

  12. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  13. Inter- and intra-industry variations of capital structure in the Czech manufacturing industry

    Directory of Open Access Journals (Sweden)

    Pavlína Pinková

    2013-01-01

    Full Text Available The objective of the paper is to investigate the existence of inter-industry variations in the capital structure of enterprises of the Czech manufacturing industry and to identify the intra-industry causes of these differences. Three measures of capital structure are employed to determine the inter-industry variations. These are total debt ratio, long-term debt and short-term debt ratios. The set of explanatory variables is included to clarify the intra-industry variations. These explanatory variables are size, asset structure, asset utilization, profitability, non-debt tax shield and growth. The paper reports the analysis of capital structure of five distinctive industrial branches, namely the manufacture of beverages, the manufacture of textiles, the manufacture of paper and paper products, the manufacture of chemicals and chemical products, and the manufacture of computer, electronic and optical products. The data come from the financial statements of selected companies and cover a period from 2008 to 2012. The analysis of variance, correlation and regression analyses are used to develop the statistical framework. The paper aims to study the impact of industry and firm characteristics on capital structure choice.

  14. Intraspecific phytochemical variation shapes community and population structure for specialist caterpillars.

    Science.gov (United States)

    Glassmire, Andrea E; Jeffrey, Christopher S; Forister, Matthew L; Parchman, Thomas L; Nice, Chris C; Jahner, Joshua P; Wilson, Joseph S; Walla, Thomas R; Richards, Lora A; Smilanich, Angela M; Leonard, Michael D; Morrison, Colin R; Simbaña, Wilmer; Salagaje, Luis A; Dodson, Craig D; Miller, Jim S; Tepe, Eric J; Villamarin-Cortez, Santiago; Dyer, Lee A

    2016-10-01

    Chemically mediated plant-herbivore interactions contribute to the diversity of terrestrial communities and the diversification of plants and insects. While our understanding of the processes affecting community structure and evolutionary diversification has grown, few studies have investigated how trait variation shapes genetic and species diversity simultaneously in a tropical ecosystem. We investigated secondary metabolite variation among subpopulations of a single plant species, Piper kelleyi (Piperaceae), using high-performance liquid chromatography (HPLC), to understand associations between plant phytochemistry and host-specialized caterpillars in the genus Eois (Geometridae: Larentiinae) and associated parasitoid wasps and flies. In addition, we used a genotyping-by-sequencing approach to examine the genetic structure of one abundant caterpillar species, Eois encina, in relation to host phytochemical variation. We found substantive concentration differences among three major secondary metabolites, and these differences in chemistry predicted caterpillar and parasitoid community structure among host plant populations. Furthermore, E. encina populations located at high elevations were genetically different from other populations. They fed on plants containing high concentrations of prenylated benzoic acid. Thus, phytochemistry potentially shapes caterpillar and wasp community composition and geographic variation in species interactions, both of which can contribute to diversification of plants and insects. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  15. Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships

    International Nuclear Information System (INIS)

    Kim, K.H.; Martin, Y.; Otis, E.; Mao, J.

    1989-01-01

    Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125 I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids

  16. Composite Elements for Biomimetic Aerospace Structures with Progressive Shape Variation Capabilities

    Directory of Open Access Journals (Sweden)

    Alessandro Airoldi

    2016-07-01

    Full Text Available The paper presents some engineering solutions for the development of innovative aerodynamic surfaces with the capability of progressive shape variation. A brief introduction of the most significant issues related to the design of such morphing structures is provided. Thereafter, two types of structural solutions are presented for the design of internal compliant structures and flexible external skins. The proposed solutions exploit the properties and the manufacturing techniques of long fibre reinforced plastic in order to fulfil the severe and contradictory requirements related to the trade-off between morphing performance and load carrying capabilities.

  17. Collagen Peptides from Crucian Skin Improve Calcium Bioavailability and Structural Characterization by HPLC-ESI-MS/MS.

    Science.gov (United States)

    Hou, Tao; Liu, Yanshuang; Guo, Danjun; Li, Bo; He, Hui

    2017-10-11

    The effects of collagen peptides (CPs), which are derived from crucian skin, were investigated in a retinoic acid-induced bone loss model. The level of serum bone alkaline phosphatase (BALP) in the model group (117.65 ± 4.66 units/L) was significantly higher than those of the other three groups (P group. In addition, the bone mineral density in the 600 mg of CPs/kg group was significantly higher (femur, 0.37 ± 0.02 g/cm 2 ; tibia, 0.33 ± 0.02 g/cm 2 ) than in the model group (femur, 0.26 ± 0.01 g/cm 2 ; tibia, 0.23 ± 0.02 g/cm 2 ). The morphology results indicated bone structure improved after the treatment with CPs. Structural characterization demonstrated that Glu, Lys, and Arg play important roles in binding calcium and promoting calcium uptake. Our results indicated that CPs could promote calcium uptake and regulate bone formation.

  18. Constraints on a possible variation of the fine structure constant from galaxy cluster data

    Energy Technology Data Exchange (ETDEWEB)

    Holanda, R.F.L. [Departamento de Física, Universidade Estadual da Paraíba, 58429-500, Campina Grande – PB (Brazil); Landau, S.J.; Sánchez G, I.E. [Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, and IFIBA, CONICET, Ciudad Universitaria – PabI, Buenos Aires 1428 (Argentina); Alcaniz, J.S. [Departamento de Astronomia, Observatório Nacional, 20921-400, Rio de Janeiro – RJ (Brazil); Busti, V.C., E-mail: holanda@uepb.edu.br, E-mail: slandau@df.uba.ar, E-mail: alcaniz@on.br, E-mail: isg.cos@gmail.com, E-mail: vinicius.busti@astro.iag.usp.br [Departamento de Física Matemática, Instituto de Física, Universidade de São Paulo, CP 66318, 05508-090, São Paulo – SP (Brazil)

    2016-05-01

    We propose a new method to probe a possible time evolution of the fine structure constant α from X-ray and Sunyaev-Zel'dovich measurements of the gas mass fraction ( f {sub gas}) in galaxy clusters. Taking into account a direct relation between variations of α and violations of the distance-duality relation, we discuss constraints on α for a class of dilaton runaway models. Although not yet competitive with bounds from high- z quasar absorption systems, our constraints, considering a sample of 29 measurements of f {sub gas}, in the redshift interval 0.14 < z < 0.89, provide an independent estimate of α variation at low and intermediate redshifts. Furthermore, current and planned surveys will provide a larger amount of data and thus allow to improve the limits on α variation obtained in the present analysis.

  19. Lateral structural variation within the overlying plate and its correlation to the Tonankai earthquake

    Science.gov (United States)

    Fujie, G.; Nakanishi, A.; Park, J.; Obana, K.; Kodaira, S.; Kaneda, Y.

    2009-12-01

    Destructive interplate earthquakes have repeatedly occurred every 100-150 years beneath the Kumano-nada, off the Kii peninsula owing to the subduction of the Philippine Sea plate beneath the southwest Japan arc. The last great interplate earthquakes in this seismogenic subduction zone was the 1944 Tonankai earthquakes, and a number of coseismic slip distribution models derived from seismic and tsunami data show remarkable lateral variations along the trough axis. In 2006 and 2007, we conducted extensive wide-angle seismic refraction and reflection surveys in the entire rupture zone of the 1944 Tonankai earthquake. We designed two along-trough and two across-trench seismic survey lines and deployed a number of OBSs (Ocean Bottom Seismometers) with a spacing of 5km and fired an airgun array with a total volume of 200L at every 0.2km. The quality of the obtained wide-angle seismic record section is substantially good and we observed remarkable regional variation in the amplitude of refraction and reflection phases. For example, in some record sections, we can trace seismic signals up to the offset of more than 100 km, but in other sections, the airgun signals become dim at the offset of less than 30km. Such regional variation in the amplitude indicates the lateral variation of the seismic attenuation structure. For revealing lateral structural variation, we developed seismic structure models by the following approach. First, we applied the first arrival tomography for developing P-wave velocity structure models. Then, we imaged structural boundaries by the reflection traveltime mapping method. Finally, we developed seismic attenuation models by using raypaths and amplitude of first arrivals. Our seismic structure models showed remarkable along-trench structural variation. In the P-wave velocity models, we found a height on the subducting Philippine plate at the eastern end of the Kumano basin (south-east off Shima peninsula). In the western area (i.e. Kumano Basin

  20. Design and Engineering Strategies for Synthetic Antimicrobial Peptides

    Science.gov (United States)

    Tossi, Alessandro

    Thousands of antimicrobial peptides (AMPs) of prokaryotic, fungal, plant, or animal origin have been identified, and their potential as lead compounds for the design of novel therapeutic agents in the treatment of infection, for stimulating the immune system, or in countering septic shock has been widely recognized. Added to this is their possible use in prophylaxis of infectious diseases for animal or plant protection, for disinfection of surgical instruments or industrial surfaces, and for food preservation among other commercially important applications. Since the early eighties, AMPs have been subject to a vast number of studies aimed at understanding what determines their potency and spectrum of activities against bacterial or fungal pathogens, and at maximizing these while limiting cytotoxic activities toward host cells. Much research has also been directed toward understanding specific mechanisms of action underlying the antimicrobial activity and selectivity, to be able to redesign the peptides for optimal performance. A central theme in the mode of action of many AMPs is their dynamic interaction with biological membranes, which involves various properties of these peptides such as, among others, surface hydrophobicity and polarity, charge, structure, and induced conformational variations. These features are often intimately interconnected so that engineering peptides to independently adjust any one property in particular is not an easy task. However, solid-phase peptide synthesis allows the use of a large repertoire of nonproteinogenic amino acids that can be used in the rational design of peptides to finely tune structural and physicochemical properties and precisely probe structure-function relationships.

  1. Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics

    NARCIS (Netherlands)

    Groves, M R; Yao, Z J; Roller, P P; Burke, T R; Barford, D

    1998-01-01

    Protein tyrosine phosphatases regulate diverse cellular processes and represent important targets for therapeutic intervention in a number of diseases. The crystal structures of protein tyrosine phosphatase 1B (PTP1B) in complex with small molecule inhibitors based upon two classes of

  2. FragKB: structural and literature annotation resource of conserved peptide fragments and residues.

    Directory of Open Access Journals (Sweden)

    Ashish V Tendulkar

    Full Text Available BACKGROUND: FragKB (Fragment Knowledgebase is a repository of clusters of structurally similar fragments from proteins. Fragments are annotated with information at the level of sequence, structure and function, integrating biological descriptions derived from multiple existing resources and text mining. METHODOLOGY: FragKB contains approximately 400,000 conserved fragments from 4,800 representative proteins from PDB. Literature annotations are extracted from more than 1,700 articles and are available for over 12,000 fragments. The underlying systematic annotation workflow of FragKB ensures efficient update and maintenance of this database. The information in FragKB can be accessed through a web interface that facilitates sequence and structural visualization of fragments together with known literature information on the consequences of specific residue mutations and functional annotations of proteins and fragment clusters. FragKB is accessible online at http://ubio.bioinfo.cnio.es/biotools/fragkb/. SIGNIFICANCE: The information presented in FragKB can be used for modeling protein structures, for designing novel proteins and for functional characterization of related fragments. The current release is focused on functional characterization of proteins through inspection of conservation of the fragments.

  3. Inter-chromosomal variation in the pattern of human population genetic structure

    Directory of Open Access Journals (Sweden)

    Baye Tesfaye M

    2011-05-01

    Full Text Available Abstract Emerging technologies now make it possible to genotype hundreds of thousands of genetic variations in individuals, across the genome. The study of loci at finer scales will facilitate the understanding of genetic variation at genomic and geographic levels. We examined global and chromosomal variations across HapMap populations using 3.7 million single nucleotide polymorphisms to search for the most stratified genomic regions of human populations and linked these regions to ontological annotation and functional network analysis. To achieve this, we used five complementary statistical and genetic network procedures: principal component (PC, cluster, discriminant, fixation index (FST and network/pathway analyses. At the global level, the first two PC scores were sufficient to account for major population structure; however, chromosomal level analysis detected subtle forms of population structure within continental populations, and as many as 31 PCs were required to classify individuals into homogeneous groups. Using recommended population ancestry differentiation measures, a total of 126 regions of the genome were catalogued. Gene ontology and networks analyses revealed that these regions included the genes encoding oculocutaneous albinism II (OCA2, hect domain and RLD 2 (HERC2, ectodysplasin A receptor (EDAR and solute carrier family 45, member 2 (SLC45A2. These genes are associated with melanin production, which is involved in the development of skin and hair colour, skin cancer and eye pigmentation. We also identified the genes encoding interferon-γ (IFNG and death-associated protein kinase 1 (DAPK1, which are associated with cell death, inflammatory and immunological diseases. An in-depth understanding of these genomic regions may help to explain variations in adaptation to different environments. Our approach offers a comprehensive strategy for analysing chromosome-based population structure and differentiation, and demonstrates the

  4. Genetic and ontogenetic variation in an endangered tree structures dependent arthropod and fungal communities.

    Directory of Open Access Journals (Sweden)

    Benjamin J Gosney

    Full Text Available Plant genetic and ontogenetic variation can significantly impact dependent fungal and arthropod communities. However, little is known of the relative importance of these extended genetic and ontogenetic effects within a species. Using a common garden trial, we compared the dependent arthropod and fungal community on 222 progeny from two highly differentiated populations of the endangered heteroblastic tree species, Eucalyptus morrisbyi. We assessed arthropod and fungal communities on both juvenile and adult foliage. The community variation was related to previous levels of marsupial browsing, as well as the variation in the physicochemical properties of leaves using near-infrared spectroscopy. We found highly significant differences in community composition, abundance and diversity parameters between eucalypt source populations in the common garden, and these were comparable to differences between the distinctive juvenile and adult foliage. The physicochemical properties assessed accounted for a significant percentage of the community variation but did not explain fully the community differences between populations and foliage types. Similarly, while differences in population susceptibility to a major marsupial herbivore may result in diffuse genetic effects on the dependent community, this still did not account for the large genetic-based differences in dependent communities between populations. Our results emphasize the importance of maintaining the populations of this rare species as separate management units, as not only are the populations highly genetically structured, this variation may alter the trajectory of biotic colonization of conservation plantings.

  5. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties.

    Science.gov (United States)

    Moreau, Christophe; Cioci, Gianluca; Iannello, Marina; Laffly, Emmanuelle; Chouquet, Anne; Ferreira, Arturo; Thielens, Nicole M; Gaboriaud, Christine

    2016-11-01

    Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant 'eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi , Entamoeba histolytica , Taenia solium , Leishmania donovani and Schistosoma mansoni . Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

  6. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

    Directory of Open Access Journals (Sweden)

    Christophe Moreau

    2016-11-01

    Full Text Available Calreticulin (CRT is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant `eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

  7. GENETIC STRUCTURE OF NORWAY SPRUCE (PICEA ABIES): CONCORDANCE OF MORPHOLOGICAL AND ALLOZYMIC VARIATION.

    Science.gov (United States)

    Lagercrantz, Ulf; Ryman, Nils

    1990-02-01

    This study describes the population structure of Norway spruce (Picea abies) as revealed by protein polymorphisms and morphological variation. Electrophoretically detectable genetic variability was examined at 22 protein loci in 70 populations from the natural range of the species in Europe. Like other conifers, Norway spruce exhibits a relatively large amount of genetic variability and little differentiation among populations. Sixteen polymorphic loci (73%) segregate for a total of 51 alleles, and average heterozygosity per population is 0.115. Approximately 5% of the total genetic diversity is explained by differences between populations (G ST = 0.052), and Nei's standard genetic distance is less than 0.04 in all cases. We suggest that the population structure largely reflects relatively recent historical events related to the last glaciation and that Norway spruce is still in a process of adaptation and differentiation. There is a clear geographic pattern in the variation of allele frequencies. A major part of the allelefrequency variation can be accounted for by a few synthetic variables (principal components), and 80% of the variation of the first principal component is "explained" by latitude and longitude. The central European populations are consistently depauperate of genetic variability, most likely as an effect of severe restrictions of population size during the last glaciation. The pattern of differentiation at protein loci is very similar to that observed for seven morphological traits examined. This similarity suggests that the same evolutionary forces have acted upon both sets of characters. © 1990 The Society for the Study of Evolution.

  8. Identification of a moronecidin-like antimicrobial peptide in the venomous fish Pterois volitans: Functional and structural study of pteroicidin-α.

    Science.gov (United States)

    Houyvet, Baptiste; Bouchon-Navaro, Yolande; Bouchon, Claude; Goux, Didier; Bernay, Benoît; Corre, Erwan; Zatylny-Gaudin, Céline

    2018-01-01

    The present study characterizes for the first time an antimicrobial peptide in lionfish (Pterois volitans), a venomous fish. Using a peptidomic approach, we identified a mature piscidin in lionfish and called it pteroicidin-α. We detected an amidated form (pteroicidin-α- CONH 2 ) and a non-amidated form (pteroicidin-α-COOH), and then performed their functional and structural study. Interestingly, the two peptides displayed different antibacterial and hemolytic activity levels. Pteroicidin-α-CONH 2 was bactericidal on human pathogens like Staphylococcus aureus or Escherichia coli, as well as on the fish pathogen Aeromonas salmonicida, while pteroicidin-α-COOH only inhibited their growth. Furthermore, the two peptides induced hemolysis of red blood cells from different vertebrates, namely humans, sea bass and lesser-spotted dogfish. Hemolysis occurred with low concentrations of pteroicidin-α-CONH 2 , indicating greater toxicity of the amidated form. Circular dichroism analysis showed that both peptides adopted a helical conformation, yet with a greater α-helix content in pteroicidin-α-CONH 2 . Overall, these results suggest that amidation strongly influences pteroicidin-α by modifying its structure and its physico-chemical characteristics and by increasing its hemolytic activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Seasonal variations of radon concentrations in single-family houses with different sub-structures

    DEFF Research Database (Denmark)

    Majborn, B.

    1992-01-01

    Seasonal variations of indoor radon concentrations have been studied in 70 single-family houses selected according to the type of sub-structure and the type of soil underneath the house. Five categories of sub-structure were included - slab-on-grade, crawl space, basement, and combinations...... of basement with slab-on-grade or crawl space. Half of the houses are located on clayey till and the other half on glaciofluvial gravel. In each house radon was measured in a living room and a bedroom, in the basement if present, and in the crawl space if present and accessible. The measurements were made...... with track detectors on a quarterly basis throughout a year. For living rooms and bedrooms the seasonal variations range from being highly significant for the slab-on-grade houses to being insignificant for the crawl space houses. For basements and crawl spaces the geometric mean radon concentrations do...

  10. Influence of variations in creep curve on creep behavior of a high-temperature structure

    International Nuclear Information System (INIS)

    Hada, Kazuhiko

    1986-01-01

    It is one of the key issues for a high-temperature structural design guideline to evaluate the influence of variations in creep curve on the creep behavior of a high-temperature structure. In the present paper, a comparative evaluation was made to clarify such influence. Additional consideration was given to the influence of the relationship between creep rupture life and minimum creep rate, i.e., the Monkman-Grant's relationship, on the creep damage evaluation. The consideration suggested that the Monkman-Grant's relationship be taken into account in evaluating the creep damage behavior, especially the creep damage variations. However, it was clarified that the application of the creep damage evaluation rule of ASME B and P.V. Code Case N-47 to the ''standard case'' which was predicted from the average creep property would predict the creep damage on the safe side. (orig./GL)

  11. Apoprotein Structure and Metal Binding Characterization of a de Novo Designed Peptide, α3DIV, that Sequesters Toxic Heavy Metals.

    Science.gov (United States)

    Plegaria, Jefferson S; Dzul, Stephen P; Zuiderweg, Erik R P; Stemmler, Timothy L; Pecoraro, Vincent L

    2015-05-12

    De novo protein design is a biologically relevant approach that provides a novel process in elucidating protein folding and modeling the metal centers of metalloproteins in a completely unrelated or simplified fold. An integral step in de novo protein design is the establishment of a well-folded scaffold with one conformation, which is a fundamental characteristic of many native proteins. Here, we report the NMR solution structure of apo α3DIV at pH 7.0, a de novo designed three-helix bundle peptide containing a triscysteine motif (Cys18, Cys28, and Cys67) that binds toxic heavy metals. The structure comprises 1067 NOE restraints derived from multinuclear multidimensional NOESY, as well as 138 dihedral angles (ψ, φ, and χ1). The backbone and heavy atoms of the 20 lowest energy structures have a root mean square deviation from the mean structure of 0.79 (0.16) Å and 1.31 (0.15) Å, respectively. When compared to the parent structure α3D, the substitution of Leu residues to Cys enhanced the α-helical content of α3DIV while maintaining the same overall topology and fold. In addition, solution studies on the metalated species illustrated metal-induced stability. An increase in the melting temperatures was observed for Hg(II), Pb(II), or Cd(II) bound α3DIV by 18-24 °C compared to its apo counterpart. Further, the extended X-ray absorption fine structure analysis on Hg(II)-α3DIV produced an average Hg(II)-S bond length at 2.36 Å, indicating a trigonal T-shaped coordination environment. Overall, the structure of apo α3DIV reveals an asymmetric distorted triscysteine metal binding site, which offers a model for native metalloregulatory proteins with thiol-rich ligands that function in regulating toxic heavy metals, such as ArsR, CadC, MerR, and PbrR.

  12. Self-Assembling Peptide Surfactants A6K and A6D Adopt a-Helical Structures Useful for Membrane Protein Stabilization

    Directory of Open Access Journals (Sweden)

    Furen Zhuang

    2011-10-01

    Full Text Available Elucidation of membrane protein structures have been greatly hampered by difficulties in producing adequately large quantities of the functional protein and stabilizing them. A6D and A6K are promising solutions to the problem and have recently been used for the rapid production of membrane-bound G protein-coupled receptors (GPCRs. We propose that despite their short lengths, these peptides can adopt α-helical structures through interactions with micelles formed by the peptides themselves. These α-helices are then able to stabilize α-helical motifs which many membrane proteins contain. We also show that A6D and A6K can form β-sheets and appear as weak hydrogels at sufficiently high concentrations. Furthermore, A6D and A6K together in sodium dodecyl sulfate (SDS can form expected β-sheet structures via a surprising α-helical intermediate.

  13. Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures

    Czech Academy of Sciences Publication Activity Database

    Zoll, Sebastian; Stanchev, Stancho; Began, Jakub; Škerle, Jan; Lepšík, Martin; Peclinovská, Lucie; Majer, Pavel; Stříšovský, Kvido

    2014-01-01

    Roč. 33, č. 20 (2014), s. 2408-2421 ISSN 0261-4189 R&D Projects: GA ČR GAP305/11/1886; GA MŠk(CZ) LK11206; GA MŠk LO1302; GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : intramembrane protease * rhomboid family * rhomboid protease * structure * substrate recognition Subject RIV: CE - Biochemistry Impact factor: 10.434, year: 2014

  14. δ-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units

    KAUST Repository

    Johansson, Johan R.

    2014-02-14

    Non-natural peptides with structures and functions similar to natural peptides have emerged lately in biomedical as well as nanotechnological contexts. They are interesting for pharmaceutical applications since they can adopt structures with new targeting potentials and because they are generally not prone to degradation by proteases. We report here a new set of peptidomimetics derived from δ-peptides, consisting of n units of a 1,5-disubstituted 1,2,3-triazole amino acid (5Tzl). The monomer was prepared using ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) chemistry using [RuCl2Cp]x as the catalyst, allowing for simpler purification and resulting in excellent yields. This achiral monomer was used to prepare peptide oligomers that are water soluble independent of peptide chain length. Conformational analysis and structural investigations of the oligomers were performed by 2D NOESY NMR experiments, and by quantum chemical calculations using the ωB97X-D functional. These data indicate that several conformations may co-exist with slight energetic differences. Together with their increased hydrophilicity, this feature of homo-5Tzl may prove essential for mimicking natural peptides composed of α-amino acids, where the various secondary structures are achieved by side chain effects and not by the rigidity of the peptide backbone. The improved synthetic method allows for facile variation of the 5Tzl amino acid side chains, further increasing the versatility of these compounds. A new set of non-natural peptides composed of 1,5-disubstituted 1,2,3-triazole amino acids is presented. These peptides benefit from: a) modular synthesis of the monomers, allowing variation of the side chains; b) increased solubility of the oligomers in water, irrespective of peptide length; c) flexibility of the backbone allowing these foldamers to adopt several conformations. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Structure of a retro-binding peptide inhibitor complexed with human alpha-thrombin.

    Science.gov (United States)

    Tabernero, L; Chang, C Y; Ohringer, S L; Lau, W F; Iwanowicz, E J; Han, W C; Wang, T C; Seiler, S M; Roberts, D G; Sack, J S

    1995-02-10

    The crystallographic structure of the ternary complex between human alpha-thrombin, hirugen and the peptidyl inhibitor Phe-alloThr-Phe-O-CH3, which is acylated at its N terminus with 4-guanidino butanoic acid (BMS-183507), has been determined at 2.6 A resolution. The structure reveals a unique "retro-binding" mode for this tripeptide active site inhibitor. The inhibitor binds with its alkyl-guanidine moiety in the primary specificity pocket and its two phenyl rings occupying the hydrophobic proximal and distal pockets of the thrombin active site. In this arrangement the backbone of the tripeptide forms a parallel beta-strand to the thrombin main-chain at the binding site. This is opposite to the orientation of the natural substrate, fibrinogen, and all the small active site-directed thrombin inhibitors whose bound structures have been previously reported. BMS-183507 is the first synthetic inhibitor proved to bind in a retro-binding fashion to thrombin, in a fashion similar to that of the N-terminal residues of the natural inhibitor hirudin. Furthermore, this new potent thrombin inhibitor (Ki = 17.2 nM) is selective for thrombin over other serine proteases tested and may be a template to be considered in designing hirudin-based thrombin inhibitors with interactions at the specificity pocket.

  16. Variational Monte Carlo studies of electromagnetic structure of few-body nuclei

    International Nuclear Information System (INIS)

    Schiavilla, R.

    1990-01-01

    The electromagnetic structure and dynamic response of A = 2, 3 and 4 nuclei are studied with the Variational Monte Carlo method by using wave functions based on realistic nuclear interactions. Recent results obtained for the elastic form factors of 2 H, 3 H, 3 He and 4 He, the radiative neutron capture on 3 He at thermal energies, and the reaction 4 He(e,e'p) 3 H are reported. 24 refs., 5 figs

  17. New Constraints on Spatial Variations of the Fine Structure Constant from Clusters of Galaxies

    Directory of Open Access Journals (Sweden)

    Ivan De Martino

    2016-12-01

    Full Text Available We have constrained the spatial variation of the fine structure constant using multi-frequency measurements of the thermal Sunyaev-Zeldovich effect of 618 X-ray selected clusters. Although our results are not competitive with the ones from quasar absorption lines, we improved by a factor 10 and ∼2.5 previous results from Cosmic Microwave Background power spectrum and from galaxy clusters, respectively.

  18. Structural Features Governing the Activity of Lactoferricin-Derived Peptides That Act in Synergy with Antibiotics against Pseudomonas aeruginosa In Vitro and In Vivo▿ †

    Science.gov (United States)

    Sánchez-Gómez, Susana; Japelj, Bostjan; Jerala, Roman; Moriyón, Ignacio; Fernández Alonso, Mirian; Leiva, José; Blondelle, Sylvie E.; Andrä, Jörg; Brandenburg, Klaus; Lohner, Karl; Martínez de Tejada, Guillermo

    2011-01-01

    Pseudomonas aeruginosa is naturally resistant to many antibiotics, and infections caused by this organism are a serious threat, especially to hospitalized patients. The intrinsic low permeability of P. aeruginosa to antibiotics results from the coordinated action of several mechanisms, such as the presence of restrictive porins and the expression of multidrug efflux pump systems. Our goal was to develop antimicrobial peptides with an improved bacterial membrane-permeabilizing ability, so that they enhance the antibacterial activity of antibiotics. We carried out a structure activity relationship analysis to investigate the parameters that govern the permeabilizing activity of short (8- to 12-amino-acid) lactoferricin-derived peptides. We used a new class of constitutional and sequence-dependent descriptors called PEDES (peptide descriptors from sequence) that allowed us to predict (Spearman's ρ = 0.74; P < 0.001) the permeabilizing activity of a new peptide generation. To study if peptide-mediated permeabilization could neutralize antibiotic resistance mechanisms, the most potent peptides were combined with antibiotics, and the antimicrobial activities of the combinations were determined on P. aeruginosa strains whose mechanisms of resistance to those antibiotics had been previously characterized. A subinhibitory concentration of compound P2-15 or P2-27 sensitized P. aeruginosa to most classes of antibiotics tested and counteracted several mechanisms of antibiotic resistance, including loss of the OprD porin and overexpression of several multidrug efflux pump systems. Using a mouse model of lethal infection, we demonstrated that whereas P2-15 and erythromycin were unable to protect mice when administered separately, concomitant administration of the compounds afforded long-lasting protection to one-third of the animals. PMID:20956602

  19. Structural features governing the activity of lactoferricin-derived peptides that act in synergy with antibiotics against Pseudomonas aeruginosa in vitro and in vivo.

    Science.gov (United States)

    Sánchez-Gómez, Susana; Japelj, Bostjan; Jerala, Roman; Moriyón, Ignacio; Fernández Alonso, Mirian; Leiva, José; Blondelle, Sylvie E; Andrä, Jörg; Brandenburg, Klaus; Lohner, Karl; Martínez de Tejada, Guillermo

    2011-01-01

    Pseudomonas aeruginosa is naturally resistant to many antibiotics, and infections caused by this organism are a serious threat, especially to hospitalized patients. The intrinsic low permeability of P. aeruginosa to antibiotics results from the coordinated action of several mechanisms, such as the presence of restrictive porins and the expression of multidrug efflux pump systems. Our goal was to develop antimicrobial peptides with an improved bacterial membrane-permeabilizing ability, so that they enhance the antibacterial activity of antibiotics. We carried out a structure activity relationship analysis to investigate the parameters that govern the permeabilizing activity of short (8- to 12-amino-acid) lactoferricin-derived peptides. We used a new class of constitutional and sequence-dependent descriptors called PEDES (peptide descriptors from sequence) that allowed us to predict (Spearman's ρ = 0.74; P < 0.001) the permeabilizing activity of a new peptide generation. To study if peptide-mediated permeabilization could neutralize antibiotic resistance mechanisms, the most potent peptides were combined with antibiotics, and the antimicrobial activities of the combinations were determined on P. aeruginosa strains whose mechanisms of resistance to those antibiotics had been previously characterized. A subinhibitory concentration of compound P2-15 or P2-27 sensitized P. aeruginosa to most classes of antibiotics tested and counteracted several mechanisms of antibiotic resistance, including loss of the OprD porin and overexpression of several multidrug efflux pump systems. Using a mouse model of lethal infection, we demonstrated that whereas P2-15 and erythromycin were unable to protect mice when administered separately, concomitant administration of the compounds afforded long-lasting protection to one-third of the animals.

  20. Catalytic water co-existing with a product peptide in the active site of HIV-1 protease revealed by X-ray structure analysis.

    Directory of Open Access Journals (Sweden)

    Vishal Prashar

    Full Text Available BACKGROUND: It is known that HIV-1 protease is an important target for design of antiviral compounds in the treatment of Acquired Immuno Deficiency Syndrome (AIDS. In this context, understanding the catalytic mechanism of the enzyme is of crucial importance as transition state structure directs inhibitor design. Most mechanistic proposals invoke nucleophilic attack on the scissile peptide bond by a water molecule. But such a water molecule coexisting with any ligand in the active site has not been found so far in the crystal structures. PRINCIPAL FINDINGS: We report here the first observation of the coexistence in the active site, of a water molecule WAT1, along with the carboxyl terminal product (Q product peptide. The product peptide has been generated in situ through cleavage of the full-length substrate. The N-terminal product (P product has diffused out and is replaced by a set of water molecules while the Q product is still held in the active site through hydrogen bonds. The position of WAT1, which hydrogen bonds to both the catalytic aspartates, is different from when there is no substrate bound in the active site. We propose WAT1 to be the position from where catalytic water attacks the scissile peptide bond. Comparison of structures of HIV-1 protease complexed with the same oligopeptide substrate, but at pH 2.0 and at pH 7.0 shows interesting changes in the conformation and hydrogen bonding interactions from the catalytic aspartates. CONCLUSIONS/SIGNIFICANCE: The structure is suggestive of the repositioning, during substrate binding, of the catalytic water for activation and subsequent nucleophilic attack. The structure could be a snap shot of the enzyme active site primed for the next round of catalysis. This structure further suggests that to achieve the goal of designing inhibitors mimicking the transition-state, the hydrogen-bonding pattern between WAT1 and the enzyme should be replicated.

  1. Catalytic water co-existing with a product peptide in the active site of HIV-1 protease revealed by X-ray structure analysis.

    Science.gov (United States)

    Prashar, Vishal; Bihani, Subhash; Das, Amit; Ferrer, Jean-Luc; Hosur, Madhusoodan

    2009-11-17

    It is known that HIV-1 protease is an important target for design of antiviral compounds in the treatment of Acquired Immuno Deficiency Syndrome (AIDS). In this context, understanding the catalytic mechanism of the enzyme is of crucial importance as transition state structure directs inhibitor design. Most mechanistic proposals invoke nucleophilic attack on the scissile peptide bond by a water molecule. But such a water molecule coexisting with any ligand in the active site has not been found so far in the crystal structures. We report here the first observation of the coexistence in the active site, of a water molecule WAT1, along with the carboxyl terminal product (Q product) peptide. The product peptide has been generated in situ through cleavage of the full-length substrate. The N-terminal product (P product) has diffused out and is replaced by a set of water molecules while the Q product is still held in the active site through hydrogen bonds. The position of WAT1, which hydrogen bonds to both the catalytic aspartates, is different from when there is no substrate bound in the active site. We propose WAT1 to be the position from where catalytic water attacks the scissile peptide bond. Comparison of structures of HIV-1 protease complexed with the same oligopeptide substrate, but at pH 2.0 and at pH 7.0 shows interesting changes in the conformation and hydrogen bonding interactions from the catalytic aspartates. The structure is suggestive of the repositioning, during substrate binding, of the catalytic water for activation and subsequent nucleophilic attack. The structure could be a snap shot of the enzyme active site primed for the next round of catalysis. This structure further suggests that to achieve the goal of designing inhibitors mimicking the transition-state, the hydrogen-bonding pattern between WAT1 and the enzyme should be replicated.

  2. Exploration of Structural and Functional Variations Owing to Point Mutations in α-NAGA.

    Science.gov (United States)

    Meshach Paul, D; Rajasekaran, R

    2018-03-01

    Schindler disease is a lysosomal storage disorder caused due to deficiency or defective activity of alpha-N-acetylgalactosaminidase (α-NAGA). Mutations in gene encoding α-NAGA cause wide range of diseases, characterized with mild to severe clinical features. Molecular effects of these mutations are yet to be explored in detail. Therefore, this study was focused on four missense mutations of α-NAGA namely, S160C, E325K, R329Q and R329W. Native and mutant structures of α-NAGA were analysed to determine geometrical deviations such as the contours of root mean square deviation, root mean square fluctuation, percentage of residues in allowed regions of Ramachandran plot and solvent accessible surface area, using conformational sampling technique. Additionally, global energy-minimized structures of native and mutants were further analysed to compute their intra-molecular interactions, hydrogen bond dilution and distribution of secondary structure. In addition, docking studies were also performed to determine variations in binding energies between native and mutants. The deleterious effects of mutants were evident due to variations in their active site residues pertaining to spatial conformation and flexibility, comparatively. Hence, variations exhibited by mutants, namely S160C, E325K, R329Q and R329W to that of native, consequently, lead to the detrimental effects causing Schindler disease. This study computationally explains the underlying reasons for the pathogenesis of the disease, thereby aiding future researchers in drug development and disease management.

  3. Variation and Genetic Structure in Platanus mexicana (Platanaceae along Riparian Altitudinal Gradient

    Directory of Open Access Journals (Sweden)

    Dulce M. Galván-Hernández

    2015-01-01

    Full Text Available Platanus mexicana is a dominant arboreal species of riparian ecosystems. These ecosystems are associated with altitudinal gradients that can generate genetic differences in the species, especially in the extremes of the distribution. However, studies on the altitudinal effect on genetic variation to riparian species are scarce. In Mexico, the population of P. mexicana along the Colipa River (Veracruz State grows below its reported minimum altitude range, possibly the lowest where this tree grows. This suggests that altitude might be an important factor in population genetics differentiation. We examined the genetic variation and population structuring at four sites with different altitudes (70, 200, 600 and 1700 m a.s.l. using ten inter-simple sequence repeats (ISSR markers. The highest value for Shannon index and Nei’s gene diversity was obtained at 1700 m a.s.l. (He = 0.27, Ne = 1.47, I = 0.42 and polymorphism reached the top value at the middle altitude (% p = 88.57. Analysis of molecular variance (AMOVA and STRUCTURE analysis indicated intrapopulation genetic differentiation. The arithmetic average (UPGMA dendrogram identified 70 m a.s.l. as the most genetically distant site. The genetic structuring resulted from limited gene flow and genetic drift. This is the first report of genetic variation in populations of P. mexicana in Mexico. This research highlights its importance as a dominant species, and its ecological and evolutionary implications in altitudinal gradients of riparian ecosystems.

  4. SV2: accurate structural variation genotyping and de novo mutation detection from whole genomes.

    Science.gov (United States)

    Antaki, Danny; Brandler, William M; Sebat, Jonathan

    2018-05-15

    Structural variation (SV) detection from short-read whole genome sequencing is error prone, presenting significant challenges for population or family-based studies of disease. Here, we describe SV2, a machine-learning algorithm for genotyping deletions and duplications from paired-end sequencing data. SV2 can rapidly integrate variant calls from multiple structural variant discovery algorithms into a unified call set with high genotyping accuracy and capability to detect de novo mutations. SV2 is freely available on GitHub (https://github.com/dantaki/SV2). jsebat@ucsd.edu. Supplementary data are available at Bioinformatics online.

  5. Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

    International Nuclear Information System (INIS)

    Ozorowski, Gabriel; Milton, Saskia; Luecke, Hartmut

    2013-01-01

    Structure of a 20-amino-acid peptide of AHNAK bound asymmetrically to the AnxA2–S100A10A heterotetramer (1:2:2 symmetry) provides insights into the atomic level interactions that govern this membrane-repair scaffolding complex. AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11) 2 (AnxA2) 2 )] has high affinity for several regions of its 1002-amino-acid C-terminal domain. (p11) 2 (AnxA2) 2 is often localized near the plasma membrane, and this C2-symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co-localize at the intracellular face of the plasma membrane in a Ca 2+ -dependent manner. The binding of AHNAK to (p11) 2 (AnxA2) 2 has been studied previously, and a minimal binding motif has been mapped to a 20-amino-acid peptide corresponding to residues 5654–5673 of the AHNAK C-terminal domain. Here, the 2.5 Å resolution crystal structure of this 20-amino-acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11) 2 (AnxA2) 2 . Binding of AHNAK to the surface of (p11) 2 (AnxA2) 2 is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11) 2 (AnxA2) 2 most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure-based consensus sequence allows interactions with various stretches of the AHNAK C-terminal domain, comparison

  6. Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

    Energy Technology Data Exchange (ETDEWEB)

    Ozorowski, Gabriel [University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697-3900 (United States); Milton, Saskia [University of California, Irvine, Irvine, CA 92697-3900 (United States); Luecke, Hartmut, E-mail: hudel@uci.edu [University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697-3900 (United States); University of California, Irvine, Irvine, CA 92697 (United States); University of California, Irvine, Irvine, CA 92697 (United States)

    2013-01-01

    Structure of a 20-amino-acid peptide of AHNAK bound asymmetrically to the AnxA2–S100A10A heterotetramer (1:2:2 symmetry) provides insights into the atomic level interactions that govern this membrane-repair scaffolding complex. AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11){sub 2}(AnxA2){sub 2})] has high affinity for several regions of its 1002-amino-acid C-terminal domain. (p11){sub 2}(AnxA2){sub 2} is often localized near the plasma membrane, and this C2-symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co-localize at the intracellular face of the plasma membrane in a Ca{sup 2+}-dependent manner. The binding of AHNAK to (p11){sub 2}(AnxA2){sub 2} has been studied previously, and a minimal binding motif has been mapped to a 20-amino-acid peptide corresponding to residues 5654–5673 of the AHNAK C-terminal domain. Here, the 2.5 Å resolution crystal structure of this 20-amino-acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11){sub 2}(AnxA2){sub 2}. Binding of AHNAK to the surface of (p11){sub 2}(AnxA2){sub 2} is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11){sub 2}(AnxA2){sub 2} most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure-based consensus sequence allows interactions with various

  7. Difference Discrete Variational Principles, Euler-Lagrange Cohomology and Symplectic, Multisymplectic Structures I: Difference Discrete Variational Principle

    Institute of Scientific and Technical Information of China (English)

    GUO Han-Ying,; LI Yu-Qi; WU Ke1; WANG Shi-Kun

    2002-01-01

    In this first paper of a series, we study the difference discrete variational principle in the framework of multi-parameter differential approach by regarding the forward difference as an entire geometric object in view of noncommutative differential geometry. Regarding the difference as an entire geometric object, the difference discrete version of Legendre transformation can be introduced. By virtue of this variational principle, we can discretely deal with the variation problems in both the Lagrangian and Hamiltonian formalisms to get difference discrete Euler-Lagrange equations and canonical ones for the difference discrete versions of the classical mechanics and classical field theory.

  8. The effect of polylysine on casein-kinase-2 activity is influenced by both the structure of the protein/peptide substrates and the subunit composition of the enzyme

    DEFF Research Database (Denmark)

    Meggio, F; Boldyreff, B; Marin, O

    1992-01-01

    , moreover, is variably accounted for by changes in Vmax and/or Km, depending on the structure of the peptide substrate. Maximum stimulation with all protein/peptide substrates tested requires the presence of the beta subunit, since the recombinant alpha subunit is much less responsive than CK2 holoenzyme......The mechanism by which polybasic peptides stimulate the activity of casein kinase 2 (CK2) has been studied by comparing the effect of polylysine on the phosphorylation of a variety of protein and peptide substrates by the native CK2 holoenzyme and by its recombinant catalytic alpha subunit, either...

  9. Vascular Structures of the Right Colon: Incidence and Variations with Their Clinical Implications.

    Science.gov (United States)

    Alsabilah, J; Kim, W R; Kim, N K

    2017-06-01

    There is a demand for a better understanding of the vascular structures around the right colonic area. Although right hemicolectomy with the recent concept of meticulous lymph node dissection is a standardized procedure for malignant diseases among most surgeons, variations in the actual anatomical vascular are not well understood. The aim of the present review was to present a detailed overview of the vascular variation pertinent to the surgery for right colon cancer. Medical literature was searched for the articles highlighting the vascular variation relevant to the right colon cancer surgery. Recently, there have been many detailed studies on applied surgical vascular anatomy based on cadaveric dissections, as well as radiological and intraoperative examinations to overcome misconceptions concerning the arterial supply and venous drainage to the right colon. Ileocolic artery and middle colic artery are consistently present in all patients arising from the superior mesenteric artery. Even though the ileocolic artery passes posterior to the superior mesenteric vein in most of the cases, in some cases courses anterior to the superior mesenteric artery. The right colic artery is inconsistently present ranging from 63% to 10% across different studies. Ileocolic vein and middle colic vein is always present, while the right colic vein is absent in 50% of patients. The gastrocolic trunk of Henle is present in 46%-100% patients across many studies with variation in the tributaries ranging from bipodal to tetrapodal. Commonly, it is found that the right colonic veins, including the right colic vein, middle colic vein, and superior right colic vein, share the confluence forming the gastrocolic trunk of Henle in a highly variable frequency and different forms. Understanding the incidence and variations of the vascular anatomy of right side colon is of crucial importance. Failure to recognize the variation during surgery can result in troublesome bleeding especially during

  10. Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis.

    Science.gov (United States)

    Lin, Kai; Zhang, Lanwei; Han, Xue; Meng, Zhaoxu; Zhang, Jianming; Wu, Yifan; Cheng, Dayou

    2018-03-28

    In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (casein presents an excellent source to produce ACE inhibitory peptides.

  11. Structural factors involved in the recognition of helix distortions in uv-damaged DNA by model peptides

    Energy Technology Data Exchange (ETDEWEB)

    Lang, H; Zimmer, C [Akademie der Wissenschaften der DDR, Jena. Forschungszentrum fuer Molekularbiologie und Medizin

    1977-02-28

    On the basis of our previous and present results concerning conformational changes of DNA after uv-irradiation some conclusions on the structure of DNA double helix in uv-damaged regions were drawn. From the results it appears that local distortions like denaturation or premelting should be excluded. Furthermore it was shown that the thymine dimerization strongly depends on the adjacent nucleic acid bases. By means of a strong binding effect of the oligopeptide netropsin to DNA irradiated at low uv-doses it is concluded that such local distortions in DNA together with a specific sequence-dependent variation of the conformation could act as recognition sites for endonucleases.

  12. Identification of structural traits that increase the antimicrobial activity of a chimeric peptide of human β-defensins 2 and 3.

    Science.gov (United States)

    Spudy, Björn; Sönnichsen, Frank D; Waetzig, Georg H; Grötzinger, Joachim; Jung, Sascha

    2012-10-12

    Antimicrobial peptides participate in the first line of defence of many organisms against pathogens. In humans, the family of β-defensins plays a pivotal role in innate immunity. Two human β-defensins, β-defensin-2 and -3 (HBD2 and HBD3), show substantial sequence identity and structural similarity. However, HBD3 kills Staphylococcus (S.) aureus with a 4- to 8-fold higher efficiency compared to HBD2, whereas their activities against Escherichia (E.) coli are very similar. The generation of six HBD2/HBD3-chimeric molecules led to the identification of distinct molecular regions which mediate their divergent killing properties. One of the chimeras (chimera C3) killed both E. coli and S. aureus with an even higher efficacy compared to the wild-type molecules. Due to the broad spectrum of its antimicrobial activity against many human multidrug-resistant pathogens, this HBD2/HBD3-chimeric peptide represents a promising candidate for a new class of antibiotics. In order to investigate the structural basis of its exceptional antimicrobial activity, the peptide's tertiary structure was determined by NMR spectroscopy, which allowed its direct comparison to the published structures of HBD2 and HBD3 and the identification of the activity-increasing molecular features. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Structural basis of the interaction of MbtH-like proteins, putative regulators of nonribosomal peptide biosynthesis, with adenylating enzymes.

    Science.gov (United States)

    Herbst, Dominik A; Boll, Björn; Zocher, Georg; Stehle, Thilo; Heide, Lutz

    2013-01-18

    The biosynthesis of nonribosomally formed peptides (NRPs), which include important antibiotics such as vancomycin, requires the activation of amino acids through adenylate formation. The biosynthetic gene clusters of NRPs frequently contain genes for small, so-called MbtH-like proteins. Recently, it was discovered that these MbtH-like proteins are required for some of the adenylation reactions in NRP biosynthesis, but the mechanism of their interaction with the adenylating enzymes has remained unknown. In this study, we determined the structure of SlgN1, a 3-methylaspartate-adenylating enzyme involved in the biosynthesis of the hybrid polyketide/NRP antibiotic streptolydigin. SlgN1 contains an MbtH-like domain at its N terminus, and our analysis defines the parameters required for an interaction between MbtH-like domains and an adenylating enzyme. Highly conserved tryptophan residues of the MbtH-like domain critically contribute to this interaction. Trp-25 and Trp-35 form a cleft on the surface of the MbtH-like domain, which accommodates the alanine side chain of Ala-433 of the adenylating domain. Mutation of Ala-433 to glutamate abolished the activity of SlgN1. Mutation of Ser-23 of the MbtH-like domain to tyrosine resulted in strongly reduced activity. However, the activity of this S23Y mutant could be completely restored by addition of the intact MbtH-like protein CloY from another organism. This suggests that the interface found in the structure of SlgN1 is the genuine interface between MbtH-like proteins and adenylating enzymes.

  14. The effect of beta-turn structure on the permeation of peptides across monolayers of bovine brain microvessel endothelial cells

    DEFF Research Database (Denmark)

    Sørensen, M; Steenberg, B; Knipp, G

    1997-01-01

    than the Ile-containing peptides as estimated by the log of their 1-octanol:HBSS partition coefficients (log Po/w). However, the three hydrophilic peptide pairs (Ac-TyrProXaaAspVal-NH2, Ac-TyrProXaaAsnVal-NH2, and Ac-TyrProXaaIleVal-NH2; Xaa = Gly, Ile) were found to permeate BBMEC monolayers...

  15. Novel haemoglobin-derived antimicrobial peptides from chicken (Gallus gallus) blood: purification, structural aspects and biological activity.

    Science.gov (United States)

    Vasilchenko, A S; Rogozhin, E A; Vasilchenko, A V; Kartashova, O L; Sycheva, M V

    2016-12-01

    To purify and characterize antimicrobial peptides derived from the acid extract of Gallus gallus blood cells. Two polypeptides (i.e. CHb-1 and CHb-2) with antibacterial activity were detected in the acidic extract of blood cells from chicken (G. gallus). The isolated peptides that possessed a potent antibacterial activity were purified using a two-step chromatography procedure that involved solid-phase extraction of a total protein/peptide extract followed by thin fractionation by reversed-phase high performance liquid chromatography (RP-HPLC). The molecular masses of the purified peptides were similar and were 4824·4 and 4825·2 Da, which have been measured by matrix-assisted laser desorption/ionization mass spectrometry (MALDI TOF MS). Their amino acid sequences were determined by Edman degradation and showed that the peptides were fully identical to the two fragments of G. gallus α-haemoglobin localized into different subunits (A and D respectively). The peptides were active in micromolar concentrations against Gram-negative Escherichia coli K12 TG1. Using the 1-N-phenylnaphthylamine, the FITC-dextran labelled probes and the live/dead staining allowed to show the hemocidin mode of action and estimate the pore size. In this study, for the first time, α-haemoglobin from chicken (G. gallus) has been investigated as a donor of the two high homologous native peptide fragments that possess potent antibacterial activity in vitro. These are membrane-active peptides and their mechanism of action against E. coli involves a toroidal pore formation. The obtained results expand the perception of the role of haemoglobin in a living system, describing it as a source of multifunction substances. Additionally, the data presented in this paper may contribute to the development of new, cost-effective, antimicrobial agents. © 2016 The Society for Applied Microbiology.

  16. Polar front associated variation in prokaryotic community structure in Arctic shelf seafloor.

    Science.gov (United States)

    Nguyen, Tan T; Landfald, Bjarne

    2015-01-01

    Spatial variations in composition of marine microbial communities and its causes have largely been disclosed in studies comprising rather large environmental and spatial differences. In the present study, we explored if a moderate but temporally permanent climatic division within a contiguous arctic shelf seafloor was traceable in the diversity patterns of its bacterial and archaeal communities. Soft bottom sediment samples were collected at 10 geographical locations, spanning spatial distances of up to 640 km, transecting the oceanic polar front in the Barents Sea. The northern sampling sites were generally colder, less saline, shallower, and showed higher concentrations of freshly sedimented phytopigments compared to the southern study locations. Sampling sites depicted low variation in relative abundances of taxa at class level, with persistent numerical dominance by lineages of Gamma- and Deltaproteobacteria (57-66% of bacterial sequence reads). The Archaea, which constituted 0.7-1.8% of 16S rRNA gene copy numbers in the sediment, were overwhelmingly (85.8%) affiliated with the Thaumarchaeota. Beta-diversity analyses showed the environmental variations throughout the sampling range to have a stronger impact on the structuring of both the bacterial and archaeal communities than spatial effects. While bacterial communities were significantly influenced by the combined effect of several weakly selective environmental differences, including temperature, archaeal communities appeared to be more uniquely structured by the level of freshly sedimented phytopigments.

  17. The variation of the fine-structure constant from disformal couplings

    Energy Technology Data Exchange (ETDEWEB)

    De Bruck, Carsten van; Mifsud, Jurgen [Consortium for Fundamental Physics, School of Mathematics and Statistics, University of Sheffield, Hounsfield Road, Sheffield S3 7RH (United Kingdom); Nunes, Nelson J., E-mail: c.vandebruck@sheffield.ac.uk, E-mail: jmifsud1@sheffield.ac.uk, E-mail: njnunes@fc.ul.pt [Instituto de Astrofísica e Ciências do Espaço, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, PT1749-016 Lisboa (Portugal)

    2015-12-01

    We study a theory in which the electromagnetic field is disformally coupled to a scalar field, in addition to a usual non-minimal electromagnetic coupling. We show that disformal couplings modify the expression for the fine-structure constant, α. As a result, the theory we consider can explain the non-zero reported variation in the evolution of α by purely considering disformal couplings. We also find that if matter and photons are coupled in the same way to the scalar field, disformal couplings itself do not lead to a variation of the fine-structure constant. A number of scenarios are discussed consistent with the current astrophysical, geochemical, laboratory and the cosmic microwave background radiation constraints on the cosmological evolution of α. The models presented are also consistent with the current type Ia supernovae constraints on the effective dark energy equation of state. We find that the Oklo bound in particular puts strong constraints on the model parameters. From our numerical results, we find that the introduction of a non-minimal electromagnetic coupling enhances the cosmological variation in α. Better constrained data is expected to be reported by ALMA and with the forthcoming generation of high-resolution ultra-stable spectrographs such as PEPSI, ESPRESSO, and ELT-HIRES. Furthermore, an expected increase in the sensitivity of molecular and nuclear clocks will put a more stringent constraint on the theory.

  18. The variation of the fine-structure constant from disformal couplings

    International Nuclear Information System (INIS)

    De Bruck, Carsten van; Mifsud, Jurgen; Nunes, Nelson J.

    2015-01-01

    We study a theory in which the electromagnetic field is disformally coupled to a scalar field, in addition to a usual non-minimal electromagnetic coupling. We show that disformal couplings modify the expression for the fine-structure constant, α. As a result, the theory we consider can explain the non-zero reported variation in the evolution of α by purely considering disformal couplings. We also find that if matter and photons are coupled in the same way to the scalar field, disformal couplings itself do not lead to a variation of the fine-structure constant. A number of scenarios are discussed consistent with the current astrophysical, geochemical, laboratory and the cosmic microwave background radiation constraints on the cosmological evolution of α. The models presented are also consistent with the current type Ia supernovae constraints on the effective dark energy equation of state. We find that the Oklo bound in particular puts strong constraints on the model parameters. From our numerical results, we find that the introduction of a non-minimal electromagnetic coupling enhances the cosmological variation in α. Better constrained data is expected to be reported by ALMA and with the forthcoming generation of high-resolution ultra-stable spectrographs such as PEPSI, ESPRESSO, and ELT-HIRES. Furthermore, an expected increase in the sensitivity of molecular and nuclear clocks will put a more stringent constraint on the theory

  19. Geographic variation in age structure and longevity in the nine-spined stickleback (Pungitius pungitius.

    Directory of Open Access Journals (Sweden)

    Jacquelin DeFaveri

    Full Text Available Variation in age and size of mature nine-spined sticklebacks (Pungitius pungitius within and among 16 Fennoscandian populations were assessed using skeletochronology. The average age of individuals in a given population varied from 1.7 to 4.7 years. Fish from pond populations were on average older than those from lake and marine populations, and females tended to be older than males. Reproduction in marine and lake populations commenced typically at an age of two years, whereas that in ponds at an age of three years. The maximum life span of the fish varied from 3 to 7 years. Mean body size within and among populations increased with increasing age, but the habitat and population differences in body size persisted even after accounting for variation in population age (and sex structure. Hence, the population differences in mean body size are not explainable by age differences alone. As such, much of the pronounced intraspecific variation in population age structure can be attributed to delayed maturation and extended longevity of the pond fish. The results are contrasted and discussed in the context of similar data from the three-spined stickleback (Gasterosteus aculeatus occupying the same geographic area.

  20. Complete covalent structure of statherin, a tyrosine-rich acidic peptide which inhibits calcium phosphate precipitation from human parotid saliva.

    Science.gov (United States)

    Schlesinger, D H; Hay, D I

    1977-03-10

    The complete amino acid sequence of human salivary statherin, a peptide which strongly inhibits precipitation from supersaturated calcium phosphate solutions, and therefore stabilizes supersaturated saliva, has been determined. The NH2-terminal half of this Mr=5380 (43 amino acids) polypeptide was determined by automated Edman degradations (liquid phase) on native statherin. The peptide was digested separately with trypsin, chymotrypsin, and Staphylococcus aureus protease, and the resulting peptides were purified by gel filtration. Manual Edman degradations on purified peptide fragments yielded peptides that completed the amino acid sequence through the penultimate COOH-terminal residue. These analyses, together with carboxypeptidase digestion of native statherin and of peptide fragments of statherin, established the complete sequence of the molecule. The 2 serine residues (positions 2 and 3) in statherin were identified as phosphoserine. The amino acid sequence of human salivary statherin is striking in a number of ways. The NH2-terminal one-third is highly polar and includes three polar dipeptides: H2PO3-Ser-Ser-H2PO3-Arg-Arg-, and Glu-Glu-. The COOH-terminal two-thirds of the molecule is hydrophobic, containing several repeating dipeptides: four of -Gn-Pro-, three of -Tyr-Gln-, two of -Gly-Tyr-, two of-Gln-Tyr-, and two of the tetrapeptide sequence -Pro-Tyr-Gln-Pro-. Unusual cleavage sites in the statherin sequence obtained with chymotrypsin and S. aureus protease were also noted.

  1. Variation Principles and Applications in the Study of Cell Structure and Aging

    Science.gov (United States)

    Economos, Angelos C.; Miquel, Jaime; Ballard, Ralph C.; Johnson, John E., Jr.

    1981-01-01

    In this report we have attempted to show that "some reality lies concealed in biological variation". This "reality" has its principles, laws, mechanisms, and rules, only a few of which we have sketched. A related idea we pursued was that important information may be lost in the process of ignoring frequency distributions of physiological variables (as is customary in experimental physiology and gerontology). We suggested that it may be advantageous to expand one's "statistical field of vision" beyond simple averages +/- standard deviations. Indeed, frequency distribution analysis may make visible some hidden information not evident from a simple qualitative analysis, particularly when the effect of some external factor or condition (e.g., aging, dietary chemicals) is being investigated. This was clearly illustrated by the application of distribution analysis in the study of variation in mouse liver cellular and fine structure, and may be true of fine structural studies in general. In living systems, structure and function interact in a dynamic way; they are "inseparable," unlike in technological systems or machines. Changes in fine structure therefore reflect changes in function. If such changes do not exceed a certain physiologic range, a quantitative analysis of structure will provide valuable information on quantitative changes in function that may not be possible or easy to measure directly. Because there is a large inherent variation in fine structure of cells in a given organ of an individual and among individuals, changes in fine structure can be analyzed only by studying frequency distribution curves of various structural characteristics (dimensions). Simple averages +/- S.D. do not in general reveal all information on the effect of a certain factor, because often this effect is not uniform; on the contrary, this will be apparent from distribution analysis because the form of the curves will be affected. We have also attempted to show in this chapter that

  2. Constraining spatial variations of the fine-structure constant in symmetron models

    Directory of Open Access Journals (Sweden)

    A.M.M. Pinho

    2017-06-01

    Full Text Available We introduce a methodology to test models with spatial variations of the fine-structure constant α, based on the calculation of the angular power spectrum of these measurements. This methodology enables comparisons of observations and theoretical models through their predictions on the statistics of the α variation. Here we apply it to the case of symmetron models. We find no indications of deviations from the standard behavior, with current data providing an upper limit to the strength of the symmetron coupling to gravity (log⁡β2<−0.9 when this is the only free parameter, and not able to constrain the model when also the symmetry breaking scale factor aSSB is free to vary.

  3. Prediction of individual differences in risky behavior in young adults via variations in local brain structure

    Science.gov (United States)

    Nasiriavanaki, Zahra; ArianNik, Mohsen; Abbassian, Abdolhosein; Mahmoudi, Elham; Roufigari, Neda; Shahzadi, Sohrab; Nasiriavanaki, Mohammadreza; Bahrami, Bahador

    2015-01-01

    In recent years the problem of how inter-individual differences play a role in risk-taking behavior has become a much debated issue. We investigated this problem based on the well-known balloon analog risk task (BART) in 48 healthy subjects in which participants inflate a virtual balloon opting for a higher score in the face of a riskier chance of the balloon explosion. In this study, based on a structural Voxel Based Morphometry (VBM) technique we demonstrate a significant positive correlation between BART score and size of the gray matter volume in the anterior insula in riskier subjects. Although the anterior insula is among the candidate brain areas that were involved in the risk taking behavior in fMRI studies, here based on our structural data it is the only area that was significantly related to structural variation among different subjects. PMID:26500482

  4. Fabrication and characterization of anode catalyst layers with structural variations for DMFC

    Science.gov (United States)

    Wang, Dazhi; Shi, Peng; Zhou, Peng; Mao, Qing; Liang, Junsheng; Wang, Suli; Li, Yang; Ren, Tongqun; Sun, Gongquan

    2018-04-01

    In this work, the electrohydrodynamic jet (E-Jet) Layer-by-Layer (LbL) deposition technique was employed to produce anode catalyst layer (CL) structure for direct methanol fuel cells (DMFC). The CLs with different thickness and porosity were fabricated with the control of the E-Jet deposition parameters. Then, the deposited anode CLs with structural variations were assembled to membrane electrode assemblies (MEAs). The results showed that the anode CL with higher porosity contributed higher dispersed catalyst, which further induced greater electrochemical active surface area (ESA) and higher performance. At optimized working condition the anode CL with high-dispersed catalyst of was produced using the E-Jet LbL deposition technique. It was observed that the peak power density is 72.8 mW cm‑2 for the cell having a porosity of 0.63, which has an increase of about 33% after modification of the CL structure.

  5. Seasonal and spatial variations in fish and macrocrustacean assemblage structure in Mad Island Marsh estuary, Texas

    Science.gov (United States)

    Akin, S.; Winemiller, K. O.; Gelwick, F. P.

    2003-05-01

    Fish and macrocrustacean assemblage structure was analyzed along an estuarine gradient at Mad Island Marsh (MIM), Matagorda Bay, TX, during March 1998-August 1999. Eight estuarine-dependent fish species accounted for 94% of the individual fishes collected, and three species accounted for 96% of macrocrustacean abundance. Consistent with evidence from other Gulf of Mexico estuarine studies, species richness and abundance were highest during late spring and summer, and lowest during winter and early spring. Sites near the bay supported the most individuals and species. Associations between fish abundance and environmental variables were examined with canonical correspondence analysis. The dominant gradient was associated with water depth and distance from the bay. The secondary gradient reflected seasonal variation and was associated with temperature, salinity, dissolved oxygen, and vegetation cover. At the scales examined, estuarine biota responded to seasonal variation more than spatial variation. Estuarine-dependent species dominated the fauna and were common throughout the open waters of the shallow lake during winter-early spring when water temperature and salinity were low and dissolved oxygen high. During summer-early fall, sub-optimal environmental conditions (high temperature, low DO) in upper reaches accounted for strong spatial variation in assemblage composition. Small estuarine-resident fishes and the blue crab ( Callinectes sapidus) were common in warm, shallow, vegetated inland sites during summer-fall. Estuarine-dependent species were common at deeper, more saline locations near the bay during this period. During summer, freshwater species, such as gizzard shad ( Dorosoma cepedianum) and gars ( Lepisosteus spp.), were positively associated with water depth and proximity to the bay. The distribution and abundance of fishes in MIM appear to result from the combined effects of endogenous, seasonal patterns of reproduction and migration operating on large

  6. Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, Marina E.; Fletcher, Georgina C.; O’Reilly, Nicola; Purkiss, Andrew G.; Thompson, Barry J. [Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3LY (United Kingdom); McDonald, Neil Q., E-mail: neil.mcdonald@cancer.org.uk [Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3LY (United Kingdom); Birkbeck College, University of London, Malet Street, London WC1E 7HX (United Kingdom)

    2015-03-01

    This study characterizes the interaction between the carboxy-terminal (ERLI) motif of the essential polarity protein Crb and the Pals1/Stardust PDZ-domain protein. Structures of human Pals1 PDZ with and without a Crb peptide are described, explaining the highly conserved nature of the ERLI motif and revealing a sterically blocked peptide-binding groove in the absence of ligand. Many components of epithelial polarity protein complexes possess PDZ domains that are required for protein interaction and recruitment to the apical plasma membrane. Apical localization of the Crumbs (Crb) transmembrane protein requires a PDZ-mediated interaction with Pals1 (protein-associated with Lin7, Stardust, MPP5), a member of the p55 family of membrane-associated guanylate kinases (MAGUKs). This study describes the molecular interaction between the Crb carboxy-terminal motif (ERLI), which is required for Drosophila cell polarity, and the Pals1 PDZ domain using crystallography and fluorescence polarization. Only the last four Crb residues contribute to Pals1 PDZ-domain binding affinity, with specificity contributed by conserved charged interactions. Comparison of the Crb-bound Pals1 PDZ structure with an apo Pals1 structure reveals a key Phe side chain that gates access to the PDZ peptide-binding groove. Removal of this side chain enhances the binding affinity by more than fivefold, suggesting that access of Crb to Pals1 may be regulated by intradomain contacts or by protein–protein interaction.

  7. Effects of atomic-level nano-structured hydroxyapatite on adsorption of bone morphogenetic protein-7 and its derived peptide by computer simulation.

    Science.gov (United States)

    Wang, Qun; Wang, Menghao; Lu, Xiong; Wang, Kefeng; Fang, Liming; Ren, Fuzeng; Lu, Guoming

    2017-11-09

    Hydroxyapatite (HA) is the principal inorganic component of bones and teeth and has been widely used as a bone repair material because of its good biocompatibility and bioactivity. Understanding the interactions between proteins and HA is crucial for designing biomaterials for bone regeneration. In this study, we evaluated the effects of atomic-level nano-structured HA (110) surfaces on the adsorption of bone morphogenetic protein-7 (BMP-7) and its derived peptide (KQLNALSVLYFDD) using molecular dynamics and density functional theory methods. The results indicated that the atomic-level morphology of HA significantly affected the interaction strength between proteins and HA substrates. The interactions of BMP-7 and its derived peptide with nano-concave and nano-pillar HA surfaces were stronger than those with flat or nano-groove HA surfaces. The results also revealed that if the groove size of nano-structured HA surfaces matched that of residues in the protein or peptide, these residues were likely to spread into the grooves of the nano-groove, nano-concave, and nano-pillar HA, further strengthening the interactions. These results are helpful in better understanding the adsorption behaviors of proteins onto nano-structured HA surfaces, and provide theoretical guidance for designing novel bioceramic materials for bone regeneration and tissue engineering.

  8. Structural Simulation of MHC-peptide Interactions using T-cell Epitope in Iron-acquisition Protein of N. meningitides for Vaccine Design

    Directory of Open Access Journals (Sweden)

    Namrata Mishra

    2010-12-01

    Full Text Available The present work uses a structural simulation approach to identify the potential target vaccine candidates or T cell epitopes (antigenic region that can activate T cell response in two iron acquisition proteins from Neisseria. An iron regulated outer membrane protein frpB: extracellular, [NMB1988], and a Major ferric Iron-binding protein fbpA: periplasmic, [NMB0634] critical for the survival of the pathogen in the host were used. Ten novel promiscuous epitopes from the two iron acquisition proteins were identified using bioinformatics interface. Of these epitopes, 630VQKAVGSIL638 present on frpB with high binding affinity for allele HLA*DR1 was identified with an anchor position at P2, an aliphatic residue at P4 and glycine at P6 making it thereby a potential quality choice for linking peptide-loaded MHC dynamics to T-cell activation and vaccine constructs. The feasibility and structural binding of predicted peptide to the respective HLA allele was investigated by molecular modeling and template-based structural simulation. The conformational properties of the linear peptide were investigated by molecular dynamics using GROMOS96 package and Swiss PDB viewer.

  9. Double-Stranded Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2001-01-01

    A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.......A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  10. Structural studies of polypeptides: Mechanism of immunoglobin catalysis and helix propagation in hybrid sequence, disulfide containing peptides

    Energy Technology Data Exchange (ETDEWEB)

    Storrs, Richard Wood [Univ. of California, Berkeley, CA (United States)

    1992-08-01

    Catalytic immunoglobin fragments were studied Nuclear Magnetic Resonance spectroscopy to identify amino acid residues responsible for the catalytic activity. Small, hybrid sequence peptides were analyzed for helix propagation following covalent initiation and for activity related to the protein from which the helical sequence was derived. Hydrolysis of p-nitrophenyl carbonates and esters by specific immunoglobins is thought to involve charge complementarity. The pK of the transition state analog P-nitrophenyl phosphate bound to the immunoglobin fragment was determined by 31P-NMR to verify the juxtaposition of a positively charged amino acid to the binding/catalytic site. Optical studies of immunoglobin mediated photoreversal of cis, syn cyclobutane thymine dimers implicated tryptophan as the photosensitizing chromophore. Research shows the chemical environment of a single tryptophan residue is altered upon binding of the thymine dimer. This tryptophan residue was localized to within 20 Å of the binding site through the use of a nitroxide paramagnetic species covalently attached to the thymine dimer. A hybrid sequence peptide was synthesized based on the bee venom peptide apamin in which the helical residues of apamin were replaced with those from the recognition helix of the bacteriophage 434 repressor protein. Oxidation of the disufide bonds occured uniformly in the proper 1-11, 3-15 orientation, stabilizing the 434 sequence in an α-helix. The glycine residue stopped helix propagation. Helix propagation in 2,2,2-trifluoroethanol mixtures was investigated in a second hybrid sequence peptide using the apamin-derived disulfide scaffold and the S-peptide sequence. The helix-stop signal previously observed was not observed in the NMR NOESY spectrum. Helical connectivities were seen throughout the S-peptide sequence. The apamin/S-peptide hybrid binded to the S-protein (residues 21-166 of ribonuclease A) and reconstituted enzymatic activity.

  11. Structural studies of polypeptides: Mechanism of immunoglobin catalysis and helix propagation in hybrid sequence, disulfide containing peptides

    Energy Technology Data Exchange (ETDEWEB)

    Storrs, R.W.

    1992-08-01

    Catalytic immunoglobin fragments were studied Nuclear Magnetic Resonance spectroscopy to identify amino acid residues responsible for the catalytic activity. Small, hybrid sequence peptides were analyzed for helix propagation following covalent initiation and for activity related to the protein from which the helical sequence was derived. Hydrolysis of p-nitrophenyl carbonates and esters by specific immunoglobins is thought to involve charge complementarity. The pK of the transition state analog P-nitrophenyl phosphate bound to the immunoglobin fragment was determined by [sup 31]P-NMR to verify the juxtaposition of a positively charged amino acid to the binding/catalytic site. Optical studies of immunoglobin mediated photoreversal of cis, syn cyclobutane thymine dimers implicated tryptophan as the photosensitizing chromophore. Research shows the chemical environment of a single tryptophan residue is altered upon binding of the thymine dimer. This tryptophan residue was localized to within 20 [Angstrom] of the binding site through the use of a nitroxide paramagnetic species covalently attached to the thymine dimer. A hybrid sequence peptide was synthesized based on the bee venom peptide apamin in which the helical residues of apamin were replaced with those from the recognition helix of the bacteriophage 434 repressor protein. Oxidation of the disufide bonds occured uniformly in the proper 1-11, 3-15 orientation, stabilizing the 434 sequence in an [alpha]-helix. The glycine residue stopped helix propagation. Helix propagation in 2,2,2-trifluoroethanol mixtures was investigated in a second hybrid sequence peptide using the apamin-derived disulfide scaffold and the S-peptide sequence. The helix-stop signal previously observed was not observed in the NMR NOESY spectrum. Helical connectivities were seen throughout the S-peptide sequence. The apamin/S-peptide hybrid binded to the S-protein (residues 21-166 of ribonuclease A) and reconstituted enzymatic activity.

  12. A cross-coupled-structure-based temperature sensor with reduced process variation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Tie Meng; Cheng Xu, E-mail: tiemeng@mprc.pku.edu.c [Microprocessor Research and Development Center, Peking University, Beijing 100871 (China)

    2009-04-15

    An innovative, thermally-insensitive phenomenon of cascaded cross-coupled structures is found. And a novel CMOS temperature sensor based on a cross-coupled structure is proposed. This sensor consists of two different ring oscillators. The first ring oscillator generates pulses that have a period, changing linearly with temperature. Instead of using the system clock like in traditional sensors, the second oscillator utilizes a cascaded cross-coupled structure to generate temperature independent pulses to capture the result from the first oscillator. Due to the compensation between the two ring oscillators, errors caused by supply voltage variations and systematic process variations are reduced. The layout design of the sensor is based on the TSMC13G process standard cell library. Only three inverters are modified for proper channel width tuning without any other custom design. This allows for an easy integration of the sensor into cell-based chips. Post-layout simulations results show that an error lower than +-1.1 deg. C can be achieved in the full temperature range from -40 to 120 deg. C. As shown by SPICE simulations, the thermal insensitivity of the cross-coupled inverters can be realized for various TSMC technologies: 0.25 mum, 0.18 mum, 0.13 mum, and 65 nm.

  13. Analyzing structural variations along strike in a deep-water thrust belt

    Science.gov (United States)

    Totake, Yukitsugu; Butler, Robert W. H.; Bond, Clare E.; Aziz, Aznan

    2018-03-01

    We characterize a deep-water fold-thrust arrays imaged by a high-resolution 3D seismic dataset in the offshore NW Borneo, Malaysia, to understand the kinematics behind spatial arrangement of structural variations throughout the fold-thrust system. The seismic volume used covers two sub-parallel fold trains associated with a series of fore-thrusts and back-thrusts. We measured fault heave, shortening value, fold geometries (forelimb dip, interlimb angle and crest depth) along strike in individual fold trains. Heave plot on strike projection allows to identify individual thrust segments showing semi-elliptical to triangular to bimodal patterns, and linkages of these segments. The linkage sites are marked by local minima in cumulative heave. These local heave minima are compensated by additional structures, such as small imbricate thrusts and tight folds indicated by large forelimb dip and small interlimb angle. Complementary profiles of the shortening amount for the two fold trains result in smoother gradient of total shortening across the structures. We interpret this reflects kinematic interaction between two fold-thrust trains. This type of along-strike variation analysis provides comprehensive understanding of a fold-thrust system and may provide an interpretative strategy for inferring the presence of complex multiple faults in less well-imaged parts of seismic volumes.

  14. Beyond sex differences: new approaches for thinking about variation in brain structure and function.

    Science.gov (United States)

    Joel, Daphna; Fausto-Sterling, Anne

    2016-02-19

    In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. © 2016 The Author(s).

  15. Phosphorylation variation during the cell cycle scales with structural propensities of proteins.

    Directory of Open Access Journals (Sweden)

    Stefka Tyanova

    Full Text Available Phosphorylation at specific residues can activate a protein, lead to its localization to particular compartments, be a trigger for protein degradation and fulfill many other biological functions. Protein phosphorylation is increasingly being studied at a large scale and in a quantitative manner that includes a temporal dimension. By contrast, structural properties of identified phosphorylation sites have so far been investigated in a static, non-quantitative way. Here we combine for the first time dynamic properties of the phosphoproteome with protein structural features. At six time points of the cell division cycle we investigate how the variation of the amount of phosphorylation correlates with the protein structure in the vicinity of the modified site. We find two distinct phosphorylation site groups: intrinsically disordered regions tend to contain sites with dynamically varying levels, whereas regions with predominantly regular secondary structures retain more constant phosphorylation levels. The two groups show preferences for different amino acids in their kinase recognition motifs - proline and other disorder-associated residues are enriched in the former group and charged residues in the latter. Furthermore, these preferences scale with the degree of disorderedness, from regular to irregular and to disordered structures. Our results suggest that the structural organization of the region in which a phosphorylation site resides may serve as an additional control mechanism. They also imply that phosphorylation sites are associated with different time scales that serve different functional needs.

  16. Geographically structured genetic variation in the Medicago lupulina-Ensifer mutualism.

    Science.gov (United States)

    Harrison, Tia L; Wood, Corlett W; Heath, Katy D; Stinchcombe, John R

    2017-07-01

    Gene flow between genetically differentiated populations can maintain variation in species interactions, especially when population structure is congruent between interacting species. However, large-scale empirical comparisons of the population structure of interacting species are rare, particularly in positive interspecific interactions (mutualisms). One agriculturally and ecologically important mutualism is the partnership between legume plants and rhizobia. Through characterizing and comparing the population genomic structure of the legume Medicago lupulina and two rhizobial species (Ensifer medicae and E. meliloti), we explored the spatial scale of population differentiation between interacting partners in their introduced range in North America. We found high proportions of E. meliloti in southeastern populations and high proportions of E. medicae in northwestern populations. Medicago lupulina and the Ensifer genus showed similar patterns of spatial genetic structure (isolation by distance). However, we detected no evidence of isolation by distance or population structure within either species of bacteria. Genome-wide nucleotide diversity within each of the two Ensifer species was low, suggesting limited introduction of strains, founder events, or severe bottlenecks. Our results suggest that there is potential for geographically structured coevolution between M. lupulina and the Ensifer genus, but not between M. lupulina and either Ensifer species. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  17. The impact of model peptides on structural and dynamic properties of egg yolk lecithin liposomes - experimental and DFT studies.

    Science.gov (United States)

    Wałęsa, Roksana; Man, Dariusz; Engel, Grzegorz; Siodłak, Dawid; Kupka, Teobald; Ptak, Tomasz; Broda, Małgorzata A

    2015-07-01

    Electron spin resonance (ESR), (1) H-NMR, voltage and resistance experiments were performed to explore structural and dynamic changes of Egg Yolk Lecithin (EYL) bilayer upon addition of model peptides. Two of them are phenylalanine (Phe) derivatives, Ac-Phe-NHMe (1) and Ac-Phe-NMe2 (2), and the third one, Ac-(Z)-ΔPhe-NMe2 (3), is a derivative of (Z)-α,β-dehydrophenylalanine. The ESR results revealed that all compounds reduced the fluidity of liposome's membrane, and the highest activity was observed for compound 2 with N-methylated C-terminal amide bond (Ac-Phe-NMe2 ). This compound, being the most hydrophobic, penetrates easily through biological membranes. This was also observed in voltage and resistance studies. (1) H-NMR studies provided a sound evidence on H-bond interactions between the studied diamides and lecithin polar head. The most significant changes in H-atom chemical shifts and spin-lattice relaxation times T1 were observed for compound 1. Our experimental studies were supported by theoretical calculations. Complexes EYLAc-Phe-NMe2 and EYLAc-(Z)-ΔPhe-NMe2 , stabilized by NH⋅⋅⋅O or/and CH⋅⋅⋅O H-bonds were created and optimized at M06-2X/6-31G(d) level of theory in vacuo and in H2 O environment. According to our molecular-modeling studies, the most probable lecithin site of H-bond interaction with studied diamides is the negatively charged O-atom in phosphate group which acts as H-atom acceptor. Moreover, the highest binding energy to hydrocarbon chains were observed in the case of Ac-Phe-NMe2 (2). Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

  18. Structure-activity studies of RFamide peptides reveal subtype-selective activation of neuropeptide FF1 and FF2 receptors.

    Science.gov (United States)

    Findeisen, Maria; Rathmann, Daniel; Beck-Sickinger, Annette G

    2011-06-06

    Selectivity is a major issue in closely related multiligand/multireceptor systems. In this study we investigated the RFamide systems of hNPFF₁R and hNPFF₂R that bind the endogenous peptide hormones NPFF, NPAF, NPVF, and NPSF. By use of a systematic approach, we characterized the role of the C-terminal dipeptide with respect to agonistic properties using synthesized [Xaa 7]NPFF and [Xaa 8]NPFF analogues. We were able to identify only slight differences in potency upon changing the position of Arg 7, as all modifications resulted in identical behavior at the NPFF₁R and NPFF₂R. However, the C-terminal Phe 8 was able to be replaced by Trp or His with only a minor loss in potency at the NPFF₂R relative to the NPFF₁R. Analogues with shorter side chains, such as α-amino-4-guanidino butyric acid ([Agb 7]NPFF) or phenylglycine ([Phg 8]NPFF), decreased efficacy for the NPFF₁ R to 25-31 % of the maximal response, suggesting that these agonist-receptor complexes are more susceptible to structural modifications. In contrast, mutations to the conserved Asp 6.59 residue in the third extracellular loop of both receptors revealed a higher sensitivity toward the hNPFF₂R receptor than toward hNPFF₁R. These data provide new insight into the subtype-specific agonistic activation of the NPFF₁ and NPFF(2) receptors that are necessary for the development of selective agonists. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Genetic Variation in Schizophrenia Liability is Shared With Intellectual Ability and Brain Structure.

    Science.gov (United States)

    Bohlken, Marc M; Brouwer, Rachel M; Mandl, René C W; Kahn, René S; Hulshoff Pol, Hilleke E

    2016-09-01

    Alterations in intellectual ability and brain structure are important genetic markers for schizophrenia liability. How variations in these phenotypes interact with variance in schizophrenia liability due to genetic or environmental factors is an area of active investigation. Studying these genetic markers using a multivariate twin modeling approach can provide novel leads for (genetic) pathways of schizophrenia development. In a sample of 70 twins discordant for schizophrenia and 130 healthy control twins, structural equation modeling was applied to quantify unique contributions of genetic and environmental factors on human brain structure (cortical thickness, cortical surface and global white matter fractional anisotropy [FA]), intellectual ability and schizophrenia liability. In total, up to 28.1% of the genetic variance (22.8% of total variance) in schizophrenia liability was shared with intelligence quotient (IQ), global-FA, cortical thickness, and cortical surface. The strongest contributor was IQ, sharing on average 16.4% of the genetic variance in schizophrenia liability, followed by cortical thickness (6.3%), global-FA (4.7%) and cortical surface (0.5%). Furthermore, we found that up to 57.4% of the variation due to environmental factors (4.6% of total variance) in schizophrenia was shared with IQ (34.2%) and cortical surface (13.4%). Intellectual ability, FA and cortical thickness show significant and independent shared genetic variance with schizophrenia liability. This suggests that measuring brain-imaging phenotypes helps explain genetic variance in schizophrenia liability that is not captured by variation in IQ. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Geographical and organisational variation in the structure of primary care services: implications for study design.

    Science.gov (United States)

    Adams, Geoffrey; Gulliford, Martin; Ukoumunne, Obioha; Chinn, Susan; Campbell, Michael

    2003-04-01

    To evaluate the extent to which structural variation between English general practices is accounted for at higher organisational levels in the National Health Service (NHS). We analysed data for 11 structural characteristics of all general practices in England. These included characteristics of general practitioners (GPs), the practice list and the services provided by practices. A four-level random effects model was used for analysis and components of variance were estimated at the levels of practice, primary care group (PCG), health authority and region. The proportion of single-handed practices ranged from 0% to 74% at PCG level and from 14% to 43% in different regions. The proportion of practices providing diabetes services ranged from 0% to 100% at PCG level and from 71% to 96% in different regions. The list size per GP ranged from 1314 to 2704 patients per GP at PCG level and from 1721 to 2225 at regional level. Across the 11 variables analysed, components of variance at general practice level accounted for between 43% and 95% of the total variance. The PCG level accounted for between 1% and 29%, the health authority level for between 2% and 15% and the regional level for between 0% and 13% of the total variance. Adjusting for an index of deprivation and the supply of GPs gave a median 8% decrease in the sum of variance components. Geographical and organisational variation in the structure of primary care services should be considered in designing studies in health systems such as the English NHS. Stratified designs may be used to increase study efficiency, but variation between areas may sometimes compromise generalisability.

  1. Biomedical Applications of Self-Assembling Peptides

    NARCIS (Netherlands)

    Radmalekshahi, Mazda; Lempsink, Ludwijn; Amidi, Maryam; Hennink, Wim E.; Mastrobattista, Enrico

    2016-01-01

    Self-assembling peptides have gained increasing attention as versatile molecules to generate diverse supramolecular structures with tunable functionality. Because of the possibility to integrate a wide range of functional domains into self-assembling peptides including cell attachment sequences,

  2. Fast-slow continuum and reproductive strategies structure plant life-history variation worldwide

    DEFF Research Database (Denmark)

    Salguero-Gómez, Roberto; Jones, Owen R; Jongejans, Eelke

    2016-01-01

    The identification of patterns in life-history strategies across the tree of life is essential to our prediction of population persistence, extinction, and diversification. Plants exhibit a wide range of patterns of longevity, growth, and reproduction, but the general determinants of this enormous...... variation in life history are poorly understood. We use demographic data from 418 plant species in the wild, from annual herbs to supercentennial trees, to examine how growth form, habitat, and phylogenetic relationships structure plant life histories and to develop a framework to predict population...

  3. Variations of Hodge Structure Considered as an Exterior Differential System: Old and New Results

    Directory of Open Access Journals (Sweden)

    James Carlson

    2009-09-01

    Full Text Available This paper is a survey of the subject of variations of Hodge structure (VHS considered as exterior differential systems (EDS. We review developments over the last twenty-six years, with an emphasis on some key examples. In the penultimate section we present some new results on the characteristic cohomology of a homogeneous Pfaffian system. In the last section we discuss how the integrability conditions of an EDS affect the expected dimension of an integral submanifold. The paper ends with some speculation on EDS and Hodge conjecture for Calabi-Yau manifolds.

  4. The story turned upside down: Meaning effects linked to variations on narrative structure

    DEFF Research Database (Denmark)

    Bundgaard, Peer; Østergaard, Svend

    2007-01-01

    be subject to variations in view of yielding specific meaning effects. This is because the production and reception of a narrative is a dynamic process where physical forces, modal forces and intentions set up a space of possibilities for the narrative trajectory. We therefore propose a determination...... structure is indeed driven by an inverted narrative schema and each significant event in the story but one (as well as each physical paragraph but one) has its rigorously symmetrical counterpart. Moreover, this inverted schema can be explained in terms of the modal forces at stake in the narrative....

  5. Discrete variational derivative method a structure-preserving numerical method for partial differential equations

    CERN Document Server

    Furihata, Daisuke

    2010-01-01

    Nonlinear Partial Differential Equations (PDEs) have become increasingly important in the description of physical phenomena. Unlike Ordinary Differential Equations, PDEs can be used to effectively model multidimensional systems. The methods put forward in Discrete Variational Derivative Method concentrate on a new class of ""structure-preserving numerical equations"" which improves the qualitative behaviour of the PDE solutions and allows for stable computing. The authors have also taken care to present their methods in an accessible manner, which means that the book will be useful to engineer

  6. Interpopulation Variation in Contour Feather Structure Is Environmentally Determined in Great Tits

    Science.gov (United States)

    Broggi, Juli; Gamero, Anna; Hohtola, Esa; Orell, Markku; Nilsson, Jan-Åke

    2011-01-01

    Background The plumage of birds is important for flying, insulation and social communication. Contour feathers cover most of the avian body and among other functions they provide a critical insulation layer against heat loss. Feather structure and composition are known to vary among individuals, which in turn determines variation in the insulation properties of the feather. However, the extent and the proximate mechanisms underlying this variation remain unexplored. Methodology/Principal Findings We analyzed contour feather structure from two different great tit populations adapted to different winter regimes, one northern population in Oulu (Finland) and one southern population in Lund (Sweden). Great tits from the two populations differed significantly in feather structure. Birds from the northern population had a denser plumage but consisting of shorter feathers with a smaller proportion containing plumulaceous barbs, compared with conspecifics from the southern population. However, differences disappeared when birds originating from the two populations were raised and moulted in identical conditions in a common-garden experiment located in Oulu, under ad libitum nutritional conditions. All birds raised in the aviaries, including adult foster parents moulting in the same captive conditions, developed a similar feather structure. These feathers were different from that of wild birds in Oulu but similar to wild birds in Lund, the latter moulting in more benign conditions than those of Oulu. Conclusions/Significance Wild populations exposed to different conditions develop contour feather differences either due to plastic responses or constraints. Environmental conditions, such as nutrient availability during feather growth play a crucial role in determining such differences in plumage structure among populations. PMID:21949798

  7. Interpopulation variation in contour feather structure is environmentally determined in great tits.

    Directory of Open Access Journals (Sweden)

    Juli Broggi

    Full Text Available The plumage of birds is important for flying, insulation and social communication. Contour feathers cover most of the avian body and among other functions they provide a critical insulation layer against heat loss. Feather structure and composition are known to vary among individuals, which in turn determines variation in the insulation properties of the feather. However, the extent and the proximate mechanisms underlying this variation remain unexplored.We analyzed contour feather structure from two different great tit populations adapted to different winter regimes, one northern population in Oulu (Finland and one southern population in Lund (Sweden. Great tits from the two populations differed significantly in feather structure. Birds from the northern population had a denser plumage but consisting of shorter feathers with a smaller proportion containing plumulaceous barbs, compared with conspecifics from the southern population. However, differences disappeared when birds originating from the two populations were raised and moulted in identical conditions in a common-garden experiment located in Oulu, under ad libitum nutritional conditions. All birds raised in the aviaries, including adult foster parents moulting in the same captive conditions, developed a similar feather structure. These feathers were different from that of wild birds in Oulu but similar to wild birds in Lund, the latter moulting in more benign conditions than those of Oulu.Wild populations exposed to different conditions develop contour feather differences either due to plastic responses or constraints. Environmental conditions, such as nutrient availability during feather growth play a crucial role in determining such differences in plumage structure among populations.

  8. Structural Variation and Uniformity among Tetraloop-Receptor Interactions and Other Loop-Helix Interactions in RNA Crystal Structures

    Science.gov (United States)

    Wu, Li; Chai, Dinggeng; Fraser, Marie E.; Zimmerly, Steven

    2012-01-01

    Tetraloop-receptor interactions are prevalent structural units in RNAs, and include the GAAA/11-nt and GNRA-minor groove interactions. In this study, we have compiled a set of 78 nonredundant loop-helix interactions from X-ray crystal structures, and examined them for the extent of their sequence and structural variation. Of the 78 interactions in the set, only four were classical GAAA/11-nt motifs, while over half (48) were GNRA-minor groove interactions. The GNRA-minor groove interactions were not a homogeneous set, but were divided into five subclasses. The most predominant subclass is characterized by two triple base pair interactions in the minor groove, flanked by two ribose zipper contacts. This geometry may be considered the “standard” GNRA-minor groove interaction, while the other four subclasses are alternative ways to form interfaces between a minor groove and tetraloop. The remaining 26 structures in the set of 78 have loops interacting with mostly idiosyncratic receptors. Among the entire set, a number of sequence-structure correlations can be identified, which may be used as initial hypotheses in predicting three-dimensional structures from primary sequences. Conversely, other sequence patterns are not predictive; for example, GAAA loop sequences and GG/CC receptors bind to each other with three distinct geometries. Finally, we observe an example of structural evolution in group II introns, in which loop-receptor motifs are substituted for each other while maintaining the larger three-dimensional geometry. Overall, the study gives a more complete view of RNA loop-helix interactions that exist in nature. PMID:23152878

  9. Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration.

    Science.gov (United States)

    Ross, Lars A; Del Bene, Victor A; Molholm, Sophie; Jae Woo, Young; Andrade, Gizely N; Abrahams, Brett S; Foxe, John J

    2017-11-01

    Three lines of evidence motivated this study. 1) CNTNAP2 variation is associated with autism risk and speech-language development. 2) CNTNAP2 variations are associated with differences in white matter (WM) tracts comprising the speech-language circuitry. 3) Children with autism show impairment in multisensory speech perception. Here, we asked whether an autism risk-associated CNTNAP2 single nucleotide polymorphism in neurotypical adults was associated with multisensory speech perception performance, and whether such a genotype-phenotype association was mediated through white matter tract integrity in speech-language circuitry. Risk genotype at rs7794745 was associated with decreased benefit from visual speech and lower fractional anisotropy (FA) in several WM tracts (right precentral gyrus, left anterior corona radiata, right retrolenticular internal capsule). These structural connectivity differences were found to mediate the effect of genotype on audiovisual speech perception, shedding light on possible pathogenic pathways in autism and biological sources of inter-individual variation in audiovisual speech processing in neurotypicals. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Spatial Evolution of the Thickness Variations over a CFRP Laminated Structure

    Science.gov (United States)

    Davila, Yves; Crouzeix, Laurent; Douchin, Bernard; Collombet, Francis; Grunevald, Yves-Henri

    2017-10-01

    Ply thickness is one of the main drivers of the structural performance of a composite part. For stress analysis calculations (e.g., finite element analysis), composite plies are commonly considered to have a constant thickness compared to the reality (coefficients of variation up to 9% of the mean ply thickness). Unless this variability is taken into account reliable property predictions cannot be made. A modelling approach of such variations is proposed using parameters obtained from a 16-ply quasi-isotropic CFRP plate cured in an autoclave. A discrete Fourier transform algorithm is used to analyse the frequency response of the observed ply and plate thickness profiles. The model inputs, obtained by a mathematical representation of the ply thickness profiles, permit the generation of a representative stratification considering the spatial continuity of the thickness variations that are in good agreement with the real ply profiles spread over the composite part. A residual deformation FE model of the composite plate is used to illustrate the feasibility of the approach.

  11. Updated constraints on spatial variations of the fine-structure constant

    Directory of Open Access Journals (Sweden)

    A.M.M. Pinho

    2016-05-01

    Full Text Available Recent work by Webb et al. has provided indications of spatial variations of the fine-structure constant, α, at a level of a few parts per million. Using a dataset of 293 archival measurements, they further show that a dipole provides a statistically good fit to the data, a result subsequently confirmed by other authors. Here we show that a more recent dataset of dedicated measurements further constrains these variations: although there are only 10 such measurements, their uncertainties are considerably smaller. We find that a dipolar variation is still a good fit to the combined dataset, but the amplitude of such a dipole must be somewhat smaller: 8.1±1.7 ppm for the full dataset, versus 9.4±2.2 ppm for the Webb et al. data alone, both at the 68.3% confidence level. Constraints on the direction on the sky of such a dipole are also significantly improved. On the other hand the data can't yet discriminate between a pure spatial dipole and one with an additional redshift dependence.

  12. Effects of temperature variations on guided waves propagating in composite structures

    Science.gov (United States)

    Shoja, Siavash; Berbyuk, Viktor; Boström, Anders

    2016-04-01

    Effects of temperature on guided waves propagating in composite materials is a well-known problem which has been investigated in many studies. The majority of the studies is focused on effects of high temperature. Understanding the effects of low temperature has major importance in composite structures and components which are operating in cold climate conditions such as e.g. wind turbines operating in cold climate regions. In this study first the effects of temperature variations on guided waves propagating in a composite plate is investigated experimentally in a cold climate chamber. The material is a common material used to manufacture rotor blades of wind turbines. The temperature range is 25°C to -25°C and effects of temperature variations on amplitude and phase shift of the received signal are investigated. In order to apply the effects of lowering the temperature on the received signal, the Baseline Signal Stretch (BSS) method is modified and used. The modification is based on decomposing the signal into symmetric and asymmetric modes and applying two different stretch factors on each of them. Finally the results obtained based on the new method is compared with the results of application of BSS with one stretch factor and experimental measurements. Comparisons show that an improvement is obtained using the BSS with the mode decomposition method at temperature variations of more than 25°C.

  13. Lateral variation in crustal and mantle structure in Bay of Bengal based on surface wave data

    Science.gov (United States)

    Kumar, Amit; Mukhopadhyay, Sagarika; Kumar, Naresh; Baidya, P. R.

    2018-01-01

    Surface waves generated by earthquakes that occurred near Sumatra, Andaman-Nicobar Island chain and Sunda arc are used to estimate crustal and upper mantle S wave velocity structure of Bay of Bengal. Records of these seismic events at various stations located along the eastern coast of India and a few stations in the north eastern part of India are selected for such analysis. These stations lie within regional distance of the selected earthquakes. The selected events are shallow focused with magnitude greater than 5.5. Data of 65, 37, 36, 53 and 36 events recorded at Shillong, Bokaro, Visakhapatnam, Chennai and Trivandrum stations respectively are used for this purpose. The ray paths from the earthquake source to the recording stations cover different parts of the Bay of Bengal. Multiple Filtering Technique (MFT) is applied to compute the group velocities of surface waves from the available data. The dispersion curves thus obtained for this data set are within the period range of 15-120 s. Joint inversion of Rayleigh and Love wave group velocity is carried out to obtain the subsurface information in terms of variation of S wave velocity with depth. The estimated S wave velocity at a given depth and layer thickness can be considered to be an average value for the entire path covered by the corresponding ray paths. However, we observe variation in the value of S wave velocity and layer thickness from data recorded at different stations, indicating lateral variation in these two parameters. Thick deposition of sediments is observed along the paths followed by surface waves to Shillong and Bokaro stations. Sediment thickness keeps on decreasing as the surface wave paths move further south. Based on velocity variation the sedimentary layer is further divided in to three parts; on top lay unconsolidated sediment, underlain by consolidated sediment. Below this lies a layer which we consider as meta-sediments. The thickness and velocity of these layers decrease from north

  14. Crystal Structure of the Dithiol Oxidase DsbA Enzyme from Proteus Mirabilis Bound Non-covalently to an Active Site Peptide Ligand

    Science.gov (United States)

    Kurth, Fabian; Duprez, Wilko; Premkumar, Lakshmanane; Schembri, Mark A.; Fairlie, David P.; Martin, Jennifer L.

    2014-01-01

    The disulfide bond forming DsbA enzymes and their DsbB interaction partners are attractive targets for development of antivirulence drugs because both are essential for virulence factor assembly in Gram-negative pathogens. Here we characterize PmDsbA from Proteus mirabilis, a bacterial pathogen increasingly associated with multidrug resistance. PmDsbA exhibits the characteristic properties of a DsbA, including an oxidizing potential, destabilizing disulfide, acidic active site cysteine, and dithiol oxidase catalytic activity. We evaluated a peptide, PWATCDS, derived from the partner protein DsbB and showed by thermal shift and isothermal titration calorimetry that it binds to PmDsbA. The crystal structures of PmDsbA, and the active site variant PmDsbAC30S were determined to high resolution. Analysis of these structures allows categorization of PmDsbA into the DsbA class exemplified by the archetypal Escherichia coli DsbA enzyme. We also present a crystal structure of PmDsbAC30S in complex with the peptide PWATCDS. The structure shows that the peptide binds non-covalently to the active site CXXC motif, the cis-Pro loop, and the hydrophobic groove adjacent to the active site of the enzyme. This high-resolution structural data provides a critical advance for future structure-based design of non-covalent peptidomimetic inhibitors. Such inhibitors would represent an entirely new antibacterial class that work by switching off the DSB virulence assembly machinery. PMID:24831013

  15. The structure of salt bridges between Arg(+) and Glu(-) in peptides investigated with 2D-IR spectroscopy: Evidence for two distinct hydrogen-bond geometries.

    Science.gov (United States)

    Huerta-Viga, Adriana; Amirjalayer, Saeed; Domingos, Sérgio R; Meuzelaar, Heleen; Rupenyan, Alisa; Woutersen, Sander

    2015-06-07

    Salt bridges play an important role in protein folding and in supramolecular chemistry, but they are difficult to detect and characterize in solution. Here, we investigate salt bridges between glutamate (Glu(-)) and arginine (Arg(+)) using two-dimensional infrared (2D-IR) spectroscopy. The 2D-IR spectrum of a salt-bridged dimer shows cross peaks between the vibrational modes of Glu(-) and Arg(+), which provide a sensitive structural probe of Glu(-)⋯Arg(+) salt bridges. We use this probe to investigate a β-turn locked by a salt bridge, an α-helical peptide whose structure is stabilized by salt bridges, and a coiled coil that is stabilized by intra- and intermolecular salt bridges. We detect a bidentate salt bridge in the β-turn, a monodentate one in the α-helical peptide, and both salt-bridge geometries in the coiled coil. To our knowledge, this is the first time 2D-IR has been used to probe tertiary side chain interactions in peptides, and our results show that 2D-IR spectroscopy is a powerful method for investigating salt bridges in solution.

  16. C9/12 Ribbon-Like Structures in Hybrid Peptides Alternating α- and Thiazole-Based γ-Amino Acids.

    Science.gov (United States)

    Bonnel, Clément; Legrand, Baptiste; Simon, Matthieu; Martinez, Jean; Bantignies, Jean-Louis; Kang, Young Kee; Wenger, Emmanuel; Hoh, Francois; Masurier, Nicolas; Maillard, Ludovic T

    2017-12-11

    According to their restricted conformational freedom, heterocyclic γ-amino acids are usually considered to be related to Z-vinylogous γ-amino acids. In this context, oligomers alternating α-amino acids and thiazole-based γ-amino acids (ATCs) were expected to fold into a canonical 12-helical shape as described for α/γ-hybrid peptides composed of cis-α/β-unsaturated γ-amino acids. However, through a combination of X-ray crystallography, NMR spectroscopy, FTIR experiments, and DFT calculations, it was determined that the folding behavior of ATC-containing hybrid peptides is much more complex. The homochiral α/(S)-ATC sequences were unable to adopt a stable conformation, whereas the heterochiral α/(R)-ATC peptides displayed novel ribbon structures stabilized by unusual C 9/12 -bifurcated hydrogen bonds. These ribbon structures could be considered as a succession of pre-organized γ/α dipeptides and may provide the basis for designing original α-helix mimics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Reversed-phase high-performance liquid chromatographic method for the determination of peptidoglycan monomers and structurally related peptides and adamantyltripeptides.

    Science.gov (United States)

    Krstanović, Marina; Frkanec, Ruza; Vranesić, Branka; Ljevaković, Durdica; Sporec, Vesna; Tomasić, Jelka

    2002-06-25

    The reversed-phase HPLC method using UV detection was developed for the determination of (a) immunostimulating peptidoglycan monomers represented by the basic structure GlcNAc-MurNAc-L-Ala-D-isoGln-meso-DAP(omegaNH(2))-D-Ala-D-Ala (PGM) and two more lipophilic derivatives, Boc-Tyr-PGM and (Ada-1-yl)-CH(2)-CO-PGM, (b) two diastereomeric immunostimulating adamantyltripeptides L- and D-(adamant-2-yl)-Gly-L-Ala-D-isoGln and (c) peptides obtained by the enzyme hydrolyses of peptidoglycans and related peptides. The enzymes used, N-acetylmuramyl-L-alanine amidase and an L,D-aminopeptidase are present in mammalian sera and are involved in the metabolism of peptidoglycans and related peptides. Appropriate solvent systems were chosen with regard to structure and lipophilicity of each compound. As well, different gradient systems within the same solvent system had to be applied in order to achieve satisfactory separation and retention time. HPLC separation was developed with the aim to use this method for the study of the stability of the tested compounds, the purity during preparation and isolation and for following the enzyme hydrolyses.

  18. Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide.

    Science.gov (United States)

    Kristensen, Ole

    2015-11-06

    The crystal structure of the NTF2-like domain of the human Ras GTPase SH3 Binding Protein (G3BP), isoform 2, was determined at a resolution of 2.75 Å in complex with a peptide containing a FGDF sequence motif. The overall structure of the protein is highly similar to the homodimeric N-terminal domains of the G3BP1 and Rasputin proteins. Recently, a subset of G3BP interacting proteins was recognized to share a common sequence motif, FGDF. The most studied binding partners, USP10 and viral nsP3, interfere with essential G3BP functions related to assembly of cellular stress granules. Reported molecular modeling suggested that FGDF-motif containing peptides bind in an extended conformation into a hydrophobic groove on the surface of the G3BP NTF2-like domain in a manner similar to the known binding of FxFG nucleoporin repeats. The results in this paper provide evidence for a different binding mode. The FGDF peptide binds and changes conformation of the protruding N-terminal residues by providing hydrophobic interactions to a symmetry related molecule that facilitated crystallization of the G3BP2 isoform. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Structure Elucidation and Activity of Kolossin A, the D-/L-Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase.

    Science.gov (United States)

    Bode, Helge B; Brachmann, Alexander O; Jadhav, Kirtikumar B; Seyfarth, Lydia; Dauth, Christina; Fuchs, Sebastian W; Kaiser, Marcel; Waterfield, Nick R; Sack, Holger; Heinemann, Stefan H; Arndt, Hans-Dieter

    2015-08-24

    The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D-/ L-peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Interrelated chemical-microstructural-nanomechanical variations in the structural units of the cuttlebone of Sepia officinalis

    Science.gov (United States)

    North, L.; Labonte, D.; Oyen, M. L.; Coleman, M. P.; Caliskan, H. B.; Johnston, R. E.

    2017-11-01

    "Cuttlebone," the internalized shell found in all members of the cephalopod family Sepiidae, is a sophisticated buoyancy device combining high porosity with considerable strength. Using a complementary suite of characterization tools, we identified significant structural, chemical, and mechanical variations across the different structural units of the cuttlebone: the dorsal shield consists of two stiff and hard layers with prismatic mineral organization which encapsulate a more ductile and compliant layer with a lamellar structure, enriched with organic matter. A similar organization is found in the chambers, which are separated by septa, and supported by meandering plates ("pillars"). Like the dorsal shield, septa contain two layers with lamellar and prismatic organization, respectively, which differ significantly in their mechanical properties: layers with prismatic organization are a factor of three stiffer and up to a factor of ten harder than those with lamellar organization. The combination of stiff and hard, and compliant and ductile components may serve to reduce the risk of catastrophic failure, and reflect the role of organic matter for the growth process of the cuttlebone. Mechanically "weaker" units may function as sacrificial structures, ensuring a stepwise failure of the individual chambers in cases of overloading, allowing the animals to retain near-neutral buoyancy even with partially damaged cuttlebones. Our findings have implications for our understanding of the structure-property-function relationship of cuttlebone, and may help to identify novel bioinspired design strategies for light-weight yet high-strength foams.

  1. Damage detection and quantification using mode curvature variation on framed structures: analysis of the preliminary results

    Science.gov (United States)

    Iacovino, Chiara; Ditommaso, Rocco; Auletta, Gianluca; Ponzo, Felice C.

    2017-04-01

    Continuous monitoring based on vibrational identification methods is increasingly employed for the evaluation of the state of health of existing buildings after strong motion earthquake. Different damage identification methods are based on the variations of damage indices defined in terms modal (eigenfrequencies, mode shapes, and modal damping) and/or non-modal parameters. Most of simplified methods for structural health monitoring and damage detection are based on the evaluation of the dynamic characteristics evolution associated to the fundamental mode of vibration of a monitored structure. Aim of this work is the upgrade of an existing method for damage localization on framed structures during a moderate/destructive earthquake. The existing version of the method is based on the comparison of the geometric characteristics (with particular reference to the mode curvature) exhibited by the structures, related to fundamental mode of vibration, before and during an earthquake. The approach is based on the use of a nonlinear filter, the band-variable filter, based on the Stockwell Transform able to extract the nonlinear response of each mode of vibration. The new version of the method provides the possibility to quantify a possible damage occurred on the monitored structure linking the mode curvature variation with the maximum inter-story drift. This paper shows the preliminary results obtained from several simulations on nonlinear numerical models of reinforced concrete framed structures, designed for only gravity loads, without and with the presence of infill panels. Furthermore, a correlation between maximum mode curvature difference and maximum inter-story drift has been defined for the different numerical models in order to quantify the structural damage. Acknowledgements This study was partially funded by the Italian Department of Civil Protection within the project DPC-RELUIS 2016 - RS4 ''Seismic observatory of structures and health monitoring'' and by the

  2. Quantitative structure-activity relationship study of antioxidative peptide by using different sets of amino acids descriptors

    Science.gov (United States)

    Li, Yao-Wang; Li, Bo; He, Jiguo; Qian, Ping

    2011-07-01

    should be a high hydrophobic and low electronic amino acid (such as Ala, Gly, Val, and Leu); the center amino acid would be an amino acid that possesses high hydrogen bond property (such as base amino acid Arg, Lys, and His). The structural characteristics of antioxidative peptide be found in this paper may contribute to the further research of antioxidative mechanism.

  3. Hippocampal dentation: Structural variation and its association with episodic memory in healthy adults.

    Science.gov (United States)

    Fleming Beattie, Julia; Martin, Roy C; Kana, Rajesh K; Deshpande, Hrishikesh; Lee, Seongtaek; Curé, Joel; Ver Hoef, Lawrence

    2017-07-01

    While the hippocampus has long been identified as a structure integral to memory, the relationship between morphology and function has yet to be fully explained. We present an analysis of hippocampal dentation, a morphological feature previously unexplored in regard to its relationship with episodic memory. "Hippocampal dentation" in this case refers to surface convolutions, primarily present in the CA1/subiculum on the inferior aspect of the hippocampus. Hippocampal dentation was visualized using ultra-high resolution structural MRI and evaluated using a novel visual rating scale. The degree of hippocampal dentation was found to vary considerably across individuals, and was positively associated with verbal memory recall and visual memory recognition in a sample of 22 healthy adults. This study is the first to characterize the variation in hippocampal dentation in a healthy cohort and to demonstrate its association with aspects of episodic memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Conformational Effects through Hydrogen Bonding in a Constrained γ-Peptide Template: From Intraresidue Seven-Membered Rings to a Gel-Forming Sheet Structure.

    Science.gov (United States)

    Awada, Hawraà; Grison, Claire M; Charnay-Pouget, Florence; Baltaze, Jean-Pierre; Brisset, François; Guillot, Régis; Robin, Sylvie; Hachem, Ali; Jaber, Nada; Naoufal, Daoud; Yazbeck, Ogaritte; Aitken, David J

    2017-05-05

    A series of three short oligomers (di-, tri-, and tetramers) of cis-2-(aminomethyl)cyclobutane carboxylic acid, a γ-amino acid featuring a cyclobutane ring constraint, were prepared, and their conformational behavior was examined spectroscopically and by molecular modeling. In dilute solutions, these peptides showed a number of low-energy conformers, including ribbonlike structures pleated around a rarely observed series of intramolecular seven-membered hydrogen bonds. In more concentrated solutions, these interactions defer to an organized supramolecular assembly, leading to thermoreversible organogel formation notably for the tripeptide, which produced fibrillar xerogels. In the solid state, the dipeptide adopted a fully extended conformation featuring a one-dimensional network of intermolecularly H-bonded molecules stacked in an antiparallel sheet alignment. This work provides unique insight into the interplay between inter- and intramolecular H-bonded conformer topologies for the same peptide template.

  5. Modeling the blockage of Lg waves from 3-D variations in crustal structure

    Science.gov (United States)

    Sanborn, Christopher J.; Cormier, Vernon F.

    2018-05-01

    Comprised of S waves trapped in Earth's crust, the high frequency (2-10 Hz) Lg wave is important to discriminating earthquakes from explosions by comparing its amplitude and waveform to those of Pg and Pn waves. Lateral variations in crustal structure, including variations in crustal thickness, intrinsic attenuation, and scattering, affect the efficiency of Lg propagation and its consistency as a source discriminant at regional (200-1500 km) distances. To investigate the effects of laterally varying Earth structure on the efficiency of propagation of Lg and Pg, we apply a radiative transport algorithm to model complete, high-frequency (2-4 Hz), regional coda envelopes. The algorithm propagates packets of energy with ray theory through large-scale 3-D structure, and includes stochastic effects of multiple-scattering by small-scale heterogeneities within the large-scale structure. Source-radiation patterns are described by moment tensors. Seismograms of explosion and earthquake sources are synthesized in canonical models to predict effects on waveforms of paths crossing regions of crustal thinning (pull-apart basins and ocean/continent transitions) and thickening (collisional mountain belts), For paths crossing crustal thinning regions, Lg is amplified at receivers within the thinned region but strongly disrupted and attenuated at receivers beyond the thinned region. For paths crossing regions of crustal thickening, Lg amplitude is attenuated at receivers within the thickened region, but experiences little or no reduction in amplitude at receivers beyond the thickened region. The length of the Lg propagation within a thickened region and the complexity of over- and under-thrust crustal layers, can produce localized zones of Lg amplification or attenuation. Regions of intense scattering within laterally homogeneous models of the crust increase Lg attenuation but do not disrupt its coda shape.

  6. Rib Geometry Explains Variation in Dynamic Structural Response: Potential Implications for Frontal Impact Fracture Risk.

    Science.gov (United States)

    Murach, Michelle M; Kang, Yun-Seok; Goldman, Samuel D; Schafman, Michelle A; Schlecht, Stephen H; Moorhouse, Kevin; Bolte, John H; Agnew, Amanda M

    2017-09-01

    The human thorax is commonly injured in motor vehicle crashes, and despite advancements in occupant safety rib fractures are highly prevalent. The objective of this study was to quantify the ability of gross and cross-sectional geometry, separately and in combination, to explain variation of human rib structural properties. One hundred and twenty-two whole mid-level ribs from 76 fresh post-mortem human subjects were tested in a dynamic frontal impact scenario. Structural properties (peak force and stiffness) were successfully predicted (p rib cross-sectional geometry obtained via direct histological imaging (total area, cortical area, and section modulus) and were improved further when utilizing a combination of cross-sectional and gross geometry (robusticity, whole bone strength index). Additionally, preliminary application of a novel, adaptive thresholding technique, allowed for total area and robusticity to be measured on a subsample of standard clinical CT scans with varied success. These results can be used to understand variation in individual rib response to frontal loading as well as identify important geometric parameters, which could ultimately improve injury criteria as well as the biofidelity of anthropomorphic test devices (ATDs) and finite element (FE) models of the human thorax.

  7. SoftSearch: integration of multiple sequence features to identify breakpoints of structural variations.

    Directory of Open Access Journals (Sweden)

    Steven N Hart

    Full Text Available BACKGROUND: Structural variation (SV represents a significant, yet poorly understood contribution to an individual's genetic makeup. Advanced next-generation sequencing technologies are widely used to discover such variations, but there is no single detection tool that is considered a community standard. In an attempt to fulfil this need, we developed an algorithm, SoftSearch, for discovering structural variant breakpoints in Illumina paired-end next-generation sequencing data. SoftSearch combines multiple strategies for detecting SV including split-read, discordant read-pair, and unmated pairs. Co-localized split-reads and discordant read pairs are used to refine the breakpoints. RESULTS: We developed and validated SoftSearch using real and synthetic datasets. SoftSearch's key features are 1 not requiring secondary (or exhaustive primary alignment, 2 portability into established sequencing workflows, and 3 is applicable to any DNA-sequencing experiment (e.g. whole genome, exome, custom capture, etc.. SoftSearch identifies breakpoints from a small number of soft-clipped bases from split reads and a few discordant read-pairs which on their own would not be sufficient to make an SV call. CONCLUSIONS: We show that SoftSearch can identify more true SVs by combining multiple sequence features. SoftSearch was able to call clinically relevant SVs in the BRCA2 gene not reported by other tools while offering significantly improved overall performance.

  8. Structural Variation within the Amygdala and Ventromedial Prefrontal Cortex Predict Memory for Impressions in Older Adults

    Directory of Open Access Journals (Sweden)

    Brittany Shane Cassidy

    2012-08-01

    Full Text Available Research has shown that lesions to regions involved in social and emotional cognition disrupt socioemotional processing and memory. We investigated how structural variation of regions involved in socioemotional memory (ventromedial prefrontal cortex [vmPFC], amygdala, as opposed to a region implicated in explicit memory (hippocampus, affected memory for impressions in young and older adults. Anatomical MRI scans for fifteen young and fifteen older adults were obtained and reconstructed to gather information about cortical thickness and subcortical volume. Young adults had greater amygdala and hippocampus volumes than old, and thicker left vmPFC than old, although right vmPFC thickness did not differ across the age groups. Participants formed behavior-based impressions and responded to interpersonally meaningful, social but interpersonally irrelevant, or non-social prompts, and completed a memory test. Results showed that greater left amygdala volume predicted enhanced overall memory for impressions in older but not younger adults. Increased right vmPFC thickness in older, but not younger, adults correlated with enhanced memory for impressions formed in the interpersonally meaningful context. Hippocampal volume was not predictive of social memory in young or older adults. These findings demonstrate the importance of structural variation in regions linked to socioemotional processing in the retention of impressions with age, and suggest that the amygdala and vmPFC play an integral role when encoding and retrieving social information.

  9. A genome wide survey of SNP variation reveals the genetic structure of sheep breeds.

    Directory of Open Access Journals (Sweden)

    James W Kijas

    Full Text Available The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.

  10. Transducer placement for robustness to variations in boundary conditions for active structural acoustic control

    Science.gov (United States)

    Sprofera, Joseph D.; Clark, Robert L.; Cabell, Randolph H.; Gibbs, Gary P.

    2005-05-01

    Turbulent boundary layer (TBL) noise is considered a primary contribution to the interior noise present in commercial airliners. There are numerous investigations of interior noise control devoted to aircraft panels; however, practical realization is a potential challenge since physical boundary conditions are uncertain at best. In most prior studies, pinned or clamped boundary conditions were assumed; however, realistic panels likely display a range of boundary conditions between these two limits. Uncertainty in boundary conditions is a challenge for control system designers, both in terms of the compensator implemented and the location of transducers required to achieve the desired control. The impact of model uncertainties, specifically uncertain boundaries, on the selection of transducer locations for structural acoustic control is considered herein. The final goal of this work is the design of an aircraft panel structure that can reduce TBL noise transmission through the use of a completely adaptive, single-input, single-output control system. The feasibility of this goal is demonstrated through the creation of a detailed analytical solution, followed by the implementation of a test model in a transmission loss apparatus. Successfully realizing a control system robust to variations in boundary conditions can lead to the design and implementation of practical adaptive structures that could be used to control the transmission of sound to the interior of aircraft. Results from this research effort indicate it is possible to optimize the design of actuator and sensor location and aperture, minimizing the impact of boundary conditions on the desired structural acoustic control.

  11. Detection of closed influenza virus hemagglutinin fusion peptide structures in membranes by backbone {sup 13}CO-{sup 15}N rotational-echo double-resonance solid-state NMR

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Ujjayini; Xie Li; Weliky, David P., E-mail: weliky@chemistry.msu.edu [Michigan State University, Department of Chemistry (United States)

    2013-02-15

    The influenza virus fusion peptide is the N-terminal {approx}20 residues of the HA2 subunit of the hemagglutinin protein and this peptide plays a key role in the fusion of the viral and endosomal membranes during initial infection of a cell. The fusion peptide adopts N-helix/turn/C-helix structure in both detergent and membranes with reports of both open and closed interhelical topologies. In the present study, backbone {sup 13}CO-{sup 15}N REDOR solid-state NMR was applied to the membrane-associated fusion peptide to detect the distribution of interhelical distances. The data clearly showed a large fraction of closed and semi-closed topologies and were best-fitted to a mixture of two structures that do not exchange. One of the earlier open structural models may have incorrect G13 dihedral angles derived from TALOS analysis of experimentally correct {sup 13}C shifts.

  12. Structure-activity relationship of cocaine- and amphetamine-regulated transcript (CART) by peptide analogs: Importance of disulfide bridges

    Czech Academy of Sciences Publication Activity Database

    Blechová, Miroslava; Nagelová, Veronika; Demianova, Zuzana; Železná, Blanka; Maletínská, Lenka

    2012-01-01

    Roč. 18, S1 (2012), S89-S90 ISSN 1075-2617. [European Peptide Symposium /32./. 02.09.2012-07.09.2012, Athens] Institutional research plan: CEZ:AV0Z40550506 Keywords : CART * neuropeptides * cell line PC12 * anorexigenic effect Subject RIV: CE - Biochemistry

  13. Structure-activity study of macropin, a novel antimicrobial peptide from the venom of solitary bee Macropis fulvipes (Hymenoptera: Melittidae)

    Czech Academy of Sciences Publication Activity Database

    Monincová, Lenka; Veverka, Václav; Slaninová, Jiřina; Buděšínský, Miloš; Fučík, Vladimír; Bednárová, Lucie; Straka, J.; Čeřovský, Václav

    2014-01-01

    Roč. 20, č. 6 (2014), s. 375-384 ISSN 1075-2617 R&D Projects: GA ČR GA203/08/0536 Institutional support: RVO:61388963 Keywords : antimicrobial peptide * analog * wild bee venom * NMR spectroscopy * CD spectroscopy Subject RIV: CE - Biochemistry Impact factor: 1.546, year: 2014

  14. Role of Hydrophobic/Aromatic Residues on the Stability of Double-Wall β-Sheet Structures Formed by a Triblock Peptide.

    Science.gov (United States)

    Ozgur, Beytullah; Sayar, Mehmet

    2017-04-27

    -depth comparison of competing structures (zero-dimensional aggregates, short and long fibers) in the triblock peptides' assembly and show that by adjusting the length of the terminal blocks, the fiber growth can be turned on or off while keeping the nanofiber morphology intact.

  15. Normal variation in early parental sensitivity predicts child structural brain development.

    Science.gov (United States)

    Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning

    2015-10-01

    Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.

    Directory of Open Access Journals (Sweden)

    Graham M West

    Full Text Available Activation of the glucagon-like peptide-1 receptor (GLP-1R in pancreatic β-cells potentiates insulin production and is a current therapeutic target for the treatment of type 2 diabetes mellitus (T2DM. Like other class B G protein-coupled receptors (GPCRs, the GLP-1R contains an N-terminal extracellular ligand binding domain. N-terminal truncations on the peptide agonist generate antagonists capable of binding to the extracellular domain, but not capable of activating full length receptor. The main objective of this study was to use Hydrogen/deuterium exchange (HDX to identify how the amide hydrogen bonding network of peptide ligands and the extracellular domain of GLP-1R (nGLP-1R were altered by binding interactions and to then use this platform to validate direct binding events for putative GLP-1R small molecule ligands. The HDX studies presented here for two glucagon-like peptide-1 receptor (GLP-1R peptide ligands indicates that the antagonist exendin-4[9-39] is significantly destabilized in the presence of nonionic detergents as compared to the agonist exendin-4. Furthermore, HDX can detect stabilization of exendin-4 and exendin-4[9-39] hydrogen bonding networks at the N-terminal helix [Val19 to Lys27] upon binding to the N-terminal extracellular domain of GLP-1R (nGLP-1R. In addition we show hydrogen bonding network stabilization on nGLP-1R in response to ligand binding, and validate direct binding events with the extracellular domain of the receptor for putative GLP-1R small molecule ligands.

  17. Solid-State Nuclear Magnetic Resonance Investigation of the Structural Topology and Lipid Interactions of a Viral Fusion Protein Chimera Containing the Fusion Peptide and Transmembrane Domain.

    Science.gov (United States)

    Yao, Hongwei; Lee, Myungwoon; Liao, Shu-Yu; Hong, Mei

    2016-12-13

    The fusion peptide (FP) and transmembrane domain (TMD) of viral fusion proteins play important roles during virus-cell membrane fusion, by inducing membrane curvature and transient dehydration. The structure of the water-soluble ectodomain of viral fusion proteins has been extensively studied crystallographically, but the structures of the FP and TMD bound to phospholipid membranes are not well understood. We recently investigated the conformations and lipid interactions of the separate FP and TMD peptides of parainfluenza virus 5 (PIV5) fusion protein F using solid-state nuclear magnetic resonance. These studies provide structural information about the two domains when they are spatially well separated in the fusion process. To investigate how these two domains are structured relative to each other in the postfusion state, when the ectodomain forms a six-helix bundle that is thought to force the FP and TMD together in the membrane, we have now expressed and purified a chimera of the FP and TMD, connected by a Gly-Lys linker, and measured the chemical shifts and interdomain contacts of the protein in several lipid membranes. The FP-TMD chimera exhibits α-helical chemical shifts in all the membranes examined and does not cause strong curvature of lamellar membranes or membranes with negative spontaneous curvature. These properties differ qualitatively from those of the separate peptides, indicating that the FP and TMD interact with each other in the lipid membrane. However, no 13 C- 13 C cross peaks are observed in two-dimensional correlation spectra, suggesting that the two helices are not tightly associated. These results suggest that the ectodomain six-helix bundle does not propagate into the membrane to the two hydrophobic termini. However, the loosely associated FP and TMD helices are found to generate significant negative Gaussian curvature to membranes that possess spontaneous positive curvature, consistent with the notion that the FP-TMD assembly may

  18. Investigation of the structural requirements of K-Ras(G12D) selective inhibitory peptide KRpep-2d using alanine scans and cysteine bridging.

    Science.gov (United States)

    Niida, Ayumu; Sasaki, Shigekazu; Yonemori, Kazuko; Sameshima, Tomoya; Yaguchi, Masahiro; Asami, Taiji; Sakamoto, Kotaro; Kamaura, Masahiro

    2017-06-15

    A structure-activity relationship study of a K-Ras(G12D) selective inhibitory cyclic peptide, KRpep-2d was performed. Alanine scanning of KRpep-2d focusing on the cyclic moiety showed that Leu 7 , Ile 9 , and Asp 12 are the key elements for K-Ras(G12D) selective inhibition of KRpep-2d. The cysteine bridging was also examined to identify the stable analog of KRpep-2d under reductive conditions. As a result, the KRpep-2d analog (12) including mono-methylene bridging showed potent K-Ras(G12D) selective inhibition in both the presence and the absence of dithiothreitol. This means that mono-methylene bridging is an effective strategy to obtain a reduction-resistance analog of parent disulfide cyclic peptides. Peptide 12 inhibited proliferation of K-Ras(G12D)-driven cancer cells significantly. These results gave valuable information for further optimization of KRpep-2d to provide novel anti-cancer drug candidates targeting the K-Ras(G12D) mutant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Biocompatible Materials Based on Self-Assembling Peptides on Ti25Nb10Zr Alloy: Molecular Structure and Organization Investigated by Synchrotron Radiation Induced Techniques

    Directory of Open Access Journals (Sweden)

    Valeria Secchi

    2018-03-01

    Full Text Available In this work, we applied advanced Synchrotron Radiation (SR induced techniques to the study of the chemisorption of the Self Assembling Peptide EAbuK16, i.e., H-Abu-Glu-Abu-Glu-Abu-Lys-Abu-Lys-Abu-Glu-Abu-Glu-Abu-Lys-Abu-Lys-NH2 that is able to spontaneously aggregate in anti-parallel β-sheet conformation, onto annealed Ti25Nb10Zr alloy surfaces. This synthetic amphiphilic oligopeptide is a good candidate to mimic extracellular matrix for bone prosthesis, since its β-sheets stack onto each other in a multilayer oriented nanostructure with internal pores of 5–200 nm size. To prepare the biomimetic material, Ti25Nb10Zr discs were treated with aqueous solutions of EAbuK16 at different pH values. Here we present the results achieved by performing SR-induced X-ray Photoelectron Spectroscopy (SR-XPS, angle-dependent Near Edge X-ray Absorption Fine Structure (NEXAFS spectroscopy, FESEM and AFM imaging on Ti25Nb10Zr discs after incubation with self-assembling peptide solution at five different pH values, selected deliberately to investigate the best conditions for peptide immobilization.

  20. Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci

    Directory of Open Access Journals (Sweden)

    Hedges Dale J

    2012-04-01

    Full Text Available Abstract Background Autism spectrum disorders (ASD represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR. Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism. Methods As copy number variations (CNVs, particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members. Results Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several

  1. Early events elicited by bombesin and structurally related peptides in quiescent Swiss 3T3 cells. II. Changes in Na+ and Ca2+ fluxes, Na+/K+ pump activity, and intracellular pH

    International Nuclear Information System (INIS)

    Mendoza, S.A.; Schneider, J.A.; Lopez-Rivas, A.; Sinnett-Smith, J.W.; Rozengurt, E.

    1986-01-01

    The amphibian tetradecapeptide, bombesin, and structurally related peptides caused a marked increase in ouabain-sensitive 86 Rb + uptake (a measure of Na + /K + pump activity) in quiescent Swiss 3T3 cells. This effect occurred within seconds after the addition of the peptide and appeared to be mediated by an increase in Na + entry into the cells. The effect of bombesin on Na + entry and Na + /K + pump activity was concentration dependent with half-maximal stimulation occurring at 0.3-0.4 nM. The structurally related peptides litorin, gastrin-releasing peptide, and neuromedin B also stimulated ouabain-sensitive 86 Rb + uptake; the relative potencies of these peptides in stimulating the Na + /K + pump were comparable to their potencies in increasing DNA synthesis. Bombesin increased Na + influx, at least in part, through an Na + /H + antiport. The peptide augmented intracellular pH and this effect was abolished in the absence of extracellular Na + . In addition to monovalent ion transport, bombesin and the structurally related peptides rapidly increased the efflux of 45 Ca 2+ from quiescent Swiss 3T3 cells. This Ca 2+ came from an intracellular pool and the efflux was associated with a 50% decrease in total intracellular Ca 2+ . The peptides also caused a rapid increase in cytosolic free calcium concentration. Prolonged pretreatment of Swiss 3T3 cells with phorbol dibutyrate, which causes a loss of protein kinase C activity, greatly decreased the stimulation of 86 Rb + uptake and Na + entry by bombesin implicating this phosphotransferase system in the mediation of part of these responses to bombesin. Since some activation of monovalent ion transport by bombesin was seen in phorbol dibutyrate-pretreated cells, it is likely that the peptide also stimulates monovalent ion transport by a second mechanism

  2. A preliminary investigation into the genetic variation and population structure of Taenia hydatigena from Sardinia, Italy.

    Science.gov (United States)

    Boufana, Belgees; Scala, Antonio; Lahmar, Samia; Pointing, Steve; Craig, Philip S; Dessì, Giorgia; Zidda, Antonella; Pipia, Anna Paola; Varcasia, Antonio

    2015-11-30

    Cysticercosis caused by the metacestode stage of Taenia hydatigena is endemic in Sardinia. Information on the genetic variation of this parasite is important for epidemiological studies and implementation of control programs. Using two mitochondrial genes, the cytochrome c oxidase subunit 1 (cox1) and the NADH dehydrogenase subunit 1 (ND1) we investigated the genetic variation and population structure of Cysticercus tenuicollis from Sardinian intermediate hosts and compared it to that from other hosts from various geographical regions. The parsimony cox1 network analysis indicated the existence of a common lineage for T. hydatigena and the overall diversity and neutrality indices indicated demographic expansion. Using the cox1 sequences, low pairwise fixation index (Fst) values were recorded for Sardinian, Iranian and Palestinian sheep C. tenuicollis which suggested the absence of genetic differentiation. Using the ND1 sequences, C. tenuicollis from Sardinian sheep appeared to be differentiated from those of goat and pig origin. In addition, goat C. tenuicollis were genetically different from adult T. hydatigena as indicated by the statistically significant Fst value. Our results are consistent with biochemical and morphological studies that suggest the existence of variants of T. hydatigena. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Genomic structural variation contributes to phenotypic change of industrial bioethanol yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Zhang, Ke; Zhang, Li-Jie; Fang, Ya-Hong; Jin, Xin-Na; Qi, Lei; Wu, Xue-Chang; Zheng, Dao-Qiong

    2016-03-01

    Genomic structural variation (GSV) is a ubiquitous phenomenon observed in the genomes of Saccharomyces cerevisiae strains with different genetic backgrounds; however, the physiological and phenotypic effects of GSV are not well understood. Here, we first revealed the genetic characteristics of a widely used industrial S. cerevisiae strain, ZTW1, by whole genome sequencing. ZTW1 was identified as an aneuploidy strain and a large-scale GSV was observed in the ZTW1 genome compared with the genome of a diploid strain YJS329. These GSV events led to copy number variations (CNVs) in many chromosomal segments as well as one whole chromosome in the ZTW1 genome. Changes in the DNA dosage of certain functional genes directly affected their expression levels and the resultant ZTW1 phenotypes. Moreover, CNVs of large chromosomal regions triggered an aneuploidy stress in ZTW1. This stress decreased the proliferation ability and tolerance of ZTW1 to various stresses, while aneuploidy response stress may also provide some benefits to the fermentation performance of the yeast, including increased fermentation rates and decreased byproduct generation. This work reveals genomic characters of the bioethanol S. cerevisiae strain ZTW1 and suggests that GSV is an important kind of mutation that changes the traits of industrial S. cerevisiae strains. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. The rate-size trade-off structures intraspecific variation in Daphnia ambigua life history parameters.

    Science.gov (United States)

    DeLong, John P; Hanley, Torrance C

    2013-01-01

    The identification of trade-offs is necessary for understanding the evolution and maintenance of diversity. Here we employ the supply-demand (SD) body size optimization model to predict a trade-off between asymptotic body size and growth rate. We use the SD model to quantitatively predict the slope of the relationship between asymptotic body size and growth rate under high and low food regimes and then test the predictions against observations for Daphnia ambigua. Close quantitative agreement between observed and predicted slopes at both food levels lends support to the model and confirms that a 'rate-size' trade-off structures life history variation in this population. In contrast to classic life history expectations, growth and reproduction were positively correlated after controlling for the rate-size trade-off. We included 12 Daphnia clones in our study, but clone identity explained only some of the variation in life history traits. We also tested the hypothesis that growth rate would be positively related to intergenic spacer length (i.e. the growth rate hypothesis) across clones, but we found that clones with intermediate intergenic spacer lengths had larger asymptotic sizes and slower growth rates. Our results strongly support a resource-based optimization of body size following the SD model. Furthermore, because some resource allocation decisions necessarily precede others, understanding interdependent life history traits may require a more nested approach.

  5. The rate-size trade-off structures intraspecific variation in Daphnia ambigua life history parameters.

    Directory of Open Access Journals (Sweden)

    John P DeLong

    Full Text Available The identification of trade-offs is necessary for understanding the evolution and maintenance of diversity. Here we employ the supply-demand (SD body size optimization model to predict a trade-off between asymptotic body size and growth rate. We use the SD model to quantitatively predict the slope of the relationship between asymptotic body size and growth rate under high and low food regimes and then test the predictions against observations for Daphnia ambigua. Close quantitative agreement between observed and predicted slopes at both food levels lends support to the model and confirms that a 'rate-size' trade-off structures life history variation in this population. In contrast to classic life history expectations, growth and reproduction were positively correlated after controlling for the rate-size trade-off. We included 12 Daphnia clones in our study, but clone identity explained only some of the variation in life history traits. We also tested the hypothesis that growth rate would be positively related to intergenic spacer length (i.e. the growth rate hypothesis across clones, but we found that clones with intermediate intergenic spacer lengths had larger asymptotic sizes and slower growth rates. Our results strongly support a resource-based optimization of body size following the SD model. Furthermore, because some resource allocation decisions necessarily precede others, understanding interdependent life history traits may require a more nested approach.

  6. Lidar observed seasonal variation of vertical canopy structure in the Amazon evergreen forests

    Science.gov (United States)

    Tang, H.; Dubayah, R.

    2017-12-01

    Both light and water are important environmental factors governing tree growth. Responses of tropical forests to their changes are complicated and can vary substantially across different spatial and temporal scales. Of particular interest is the dry-season greening-up of Amazon forests, a phenomenon undergoing considerable debates whether it is real or a "light illusion" caused by artifacts of passive optical remote sensing techniques. Here we analyze seasonal dynamic patterns of vertical canopy structure in the Amazon forests using lidar observations from NASA's Ice, Cloud, and and land Elevation Satellite (ICESat). We found that the net greening of canopy layer coincides with the wet-to-dry transition period, and its net browning occurs mostly at the late dry season. The understory also shows a seasonal cycle, but with an opposite variation to canopy and minimal correlation to seasonal variations in rainfall or radiation. Our results further suggest a potential interaction between canopy layers in the light regime that can optimize the growth of Amazon forests during the dry season. This light regime variability that exists in both spatial and temporal domains can better reveal the dry-season greening-up phenomenon, which appears less obvious when treating the Amazon forests as a whole.

  7. Variations of magnetic properties of UH3 with modified structure and composition

    Directory of Open Access Journals (Sweden)

    M. Paukov

    2016-06-01

    Full Text Available UH3 based hydrides with modified structure and composition can be prepared using high H2 pressures from precursors in the form of rapidly cooled uranium alloys. While the alloys with α-U structure lead to the β-UH3 type of hydrides, γ-U alloys (bcc lead either to α-UH3 hydride type or nanocrystalline β-UH3. The nanocrystalline β-UH3 structure, appearing for Mo alloying, can accommodate in addition numerous other d-metal components, as Ti, Zr, Fe, Nb. The pure Mo alloyed hydrides (UH31−xMox exhibit increasing Curie temperature TC with maximum exceeding 200 K for x = 0.12–0.15. Other components added reduce the TC increment with respect to pure UH3 (170 K. Also alloying by Zr gives a weaker enhancement. Seen globally, the TC variations are rather modest, which reflects the prominence of interaction of U with H. It is suggested that important ingredient is a charge transfer, depopulating the U-6d and 7s states, while the 5f band stays at the Fermi level.

  8. AN INVESTIGATION OF THE VARIATION OF PORE STRUCTURE IN EUCALYPTUS FIBRE DURING RECYCLING

    Directory of Open Access Journals (Sweden)

    Wen Jie Guo

    2011-04-01

    Full Text Available Variation in the pore structure of eucalyptus fibre during recycling was investigated using low-temperature nitrogen adsorption, atomic force microscopy (AFM, and fractal geometry. The Brunauer- Emmett-Teller (BET surface area of the fibre fell to 55.1% of the original value after the first cycle, and to 49.0% after the second cycle, ultimately declining to 35.0% after the fourth. The Barret-Joyner- Halenda (BJH adsorption cumulative pore volume fell to 38.4% of the original by the fourth. After four cycles, the average pore diameter fell to 82% of the original. AFM tests showed that the pore structure in fibre expressed high self-similarity in statistics, and the pore structure in the fibre could be regarded as a fractal. Fractal geometry analysis of the results showed that the fractal dimension of eucalyptus virgin fibre is 2.954. With the number of process cycles increasing, the fractal dimension fell to a minimum of 2.886 after four cycles. The water retention value (WRV of the fibre was proportional to the fractal dimension and the crystallinity of fibre.

  9. Time-Dependent Variations in Structure of Sheep Wool Irradiated by Electron Beam

    Directory of Open Access Journals (Sweden)

    Zuzana Hanzlíková

    2017-01-01

    Full Text Available Wool scoured in tap water with no special degreasing and containing a balanced humidity responding to usual laboratory conditions was irradiated by accelerated electron beam in the range of 0–350 kGy dose. Time variations of the wool structure were measured using FTIR, Raman, and EPR spectroscopy. The aim was to determine whether preexposure treatment of the wool, as well as postexposure time, affects the properties of the irradiated wool. Reactive products such as S-sulfonate, cystine monoxide, cystine dioxide, cysteic acid, disulphides, and carboxylates displayed a considerable fluctuation in quantity depending on both the absorbed dose and time. Mutual transformations of S-oxidized products into cysteic acid appeared to be faster than those in dry and degreased wool assuming that the present humidity inside the fibres is decisive as an oxygen source. EPR results indicated a longer lifetime for free radicals induced by lower doses compared with the radicals generated by higher ones. The pattern of the conformational composition of the secondary structure (α-helix, β-sheet, random, and residual conformations also showed a large variability depending on absorbed dose as well as postexposure time. The most stable secondary structure was observed in nonirradiated wool but even this showed a small but observable change after a longer time, too.

  10. The band gap variation of a two dimensional binary locally resonant structure in thermal environment

    Directory of Open Access Journals (Sweden)

    Zhen Li

    2017-01-01

    Full Text Available In this study, the numerical investigation of thermal effect on band gap dynamical characteristic for a two-dimensional binary structure composed of aluminum plate periodically filled with nitrile rubber cylinder is presented. Initially, the band gap of the binary structure variation trend with increasing temperature is studied by taking the softening effect of thermal stress into account. A breakthrough is made which found the band gap being narrower and shifting to lower frequency in thermal environment. The complete band gap which in higher frequency is more sensitive to temperature that it disappears with temperature increasing. Then some new transformed models are created by changing the height of nitrile rubber cylinder from 1mm to 7mm. Simulations show that transformed model can produce a wider band gap (either flexure or complete band gap. A proper forbidden gap of elastic wave can be utilized in thermal environment although both flexure and complete band gaps become narrower with temperature. Besides that, there is a zero-frequency flat band appearing in the first flexure band, and it becomes broader with temperature increasing. The band gap width decreases trend in thermal environment, as well as the wider band gap induced by the transformed model with higher nitrile rubber cylinder is useful for the design and application of phononic crystal structures in thermal environment.

  11. Intensive Care Unit Structure Variation and Implications for Early Mobilization Practices. An International Survey.

    Science.gov (United States)

    Bakhru, Rita N; McWilliams, David J; Wiebe, Douglas J; Spuhler, Vicki J; Schweickert, William D

    2016-09-01

    Early mobilization (EM) improves outcomes for mechanically ventilated patients. Variation in structure and organizational characteristics may affect implementation of EM practices. We queried intensive care unit (ICU) environment and standardized ICU practices to evaluate organizational characteristics that enable EM practice. We recruited 151 ICUs in France, 150 in Germany, 150 in the United Kingdom, and 500 in the United States by telephone. Survey domains included respondent characteristics, hospital and ICU characteristics, and ICU practices and protocols. We surveyed 1,484 ICU leaders and received a 64% response rate (951 ICUs). Eighty-eight percent of respondents were in nursing leadership roles; the remainder were physiotherapists. Surveyed ICUs were predominantly mixed medical-surgical units (67%), and 27% were medical ICUs. ICU staffing models differed significantly (P equipment were highly variable among respondents. International ICU structure and practice is quite heterogeneous, and several factors (multidisciplinary rounds, setting daily goals for patients, presence of a dedicated physiotherapist, country, and nurse/patient staffing ratio) are significantly associated with the practice of EM. Practice and barriers may be far different based upon staffing structure. To achieve successful implementation, whether through trials or quality improvement, ICU staffing and practice patterns must be taken into account.

  12. Slope variation and population structure of tree species from different ecological groups in South Brazil.

    Science.gov (United States)

    Bianchini, Edmilson; Garcia, Cristina C; Pimenta, José A; Torezan, José M D

    2010-09-01

    Size structure and spatial arrangement of 13 abundant tree species were determined in a riparian forest fragment in Paraná State, South Brazil (23°16'S and 51°01'W). The studied species were Aspidosperma polyneuron Müll. Arg., Astronium graveolens Jacq. and Gallesia integrifolia (Spreng) Harms (emergent species); Alseis floribunda Schott, Ruprechtia laxiflora Meisn. and Bougainvillea spectabilis Willd. (shade-intolerant canopy species); Machaerium paraguariense Hassl, Myroxylum peruiferum L. and Chrysophyllum gonocarpum (Mart. & Eichler ex Miq.) Engl. (shade-tolerant canopy species); Sorocea bonplandii (Baill.) Bürger, Trichilia casaretti C. Dc, Trichilia catigua A. Juss. and Actinostemon concolor (Spreng.) Müll. Arg. (understory small trees species). Height and diameter structures and basal area of species were analyzed. Spatial patterns and slope correlation were analyzed by Moran's / spatial autocorrelation coefficient and partial Mantel test, respectively. The emergent and small understory species showed the highest and the lowest variations in height, diameter and basal area. Size distribution differed among emergent species and also among canopy shade-intolerant species. The spatial pattern ranged among species in all groups, except in understory small tree species. The slope was correlated with spatial pattern for A. polyneuron, A. graveolens, A. floribunda, R. laxiflora, M. peruiferum and T. casaretti. The results indicated that most species occurred in specific places, suggesting that niche differentiation can be an important factor in structuring the tree community.

  13. Harnessing cell-to-cell variations to probe bacterial structure and biophysics

    Science.gov (United States)

    Cass, Julie A.

    Advances in microscopy and biotechnology have given us novel insights into cellular biology and physics. While bacteria were long considered to be relatively unstructured, the development of fluorescence microscopy techniques, and spatially and temporally resolved high-throughput quantitative studies, have uncovered that the bacterial cell is highly organized, and its structure rigorously maintained. In this thesis I will describe our gateTool software, designed to harness cell-to-cell variations to probe bacterial structure, and discuss two exciting aspects of structure that we have employed gateTool to investigate: (i) chromosome organization and the cellular mechanisms for controlling DNA dynamics, and (ii) the study of cell wall synthesis, and how the genes in the synthesis pathway impact cellular shape. In the first project, we develop a spatial and temporal mapping of cell-cycle-dependent chromosomal organization, and use this quantitative map to discover that chromosomal loci segregate from midcell with universal dynamics. In the second project, I describe preliminary time- lapse and snapshot imaging analysis suggesting phentoypical coherence across peptidoglycan synthesis pathways.

  14. Study of α-crystallin structure by small-angle neutron scattering with contrast variation

    International Nuclear Information System (INIS)

    Krivandin, A.V.; Muranov, K.O.; Polyanskij, N.B.; Ostrovskij, M.A.; Murugova, T.N.; Kuklin, A.I.; Aksenov, V.L.

    2010-01-01

    The structure of the oligomeric protein α-crystallin from the bovine eye lens has been investigated by small-angle neutron scattering (SANS) by the contrast variation method (volume fraction of D 2 O was 0, 23, 68 and 90%). Experiments were carried out on YuMO spectrometer (IBR-2 reactor, JINR). From the SANS curves the match point for α-crystallin (43% D 2 O) and its average scattering length density at this point (2.4·10 10 cm -2 ) have been obtained. The radius of gyration and distance distribution functions for α-crystallin have been calculated as well. On the basis of these calculations it was concluded that α-crystallin has a homogeneous distribution of the scattering density in domains inaccessible for water penetration and all parts of this protein undergo a uniform deuteration. The latter indicates that all α-crystallin subunits have an equal accessibility for water and presumably for some other low molecular weight substances. These conclusions on the α-crystallin structure (a homogeneous distribution of the scattering density and an equal accessibility of all subunits for low molecular weight substances) should be taken into account in the time of elaboration of α-crystallin quaternary structure models

  15. NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.

    Science.gov (United States)

    Rawat, Atul; Kumar, Dinesh

    2013-01-01

    Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary H(α) chemical shifts and three bond H(N) -H(α) coupling constants indicated that most of the residues of the