Correlated binomial models and correlation structures

International Nuclear Information System (INIS)

Hisakado, Masato; Kitsukawa, Kenji; Mori, Shintaro

2006-01-01

We discuss a general method to construct correlated binomial distributions by imposing several consistent relations on the joint probability function. We obtain self-consistency relations for the conditional correlations and conditional probabilities. The beta-binomial distribution is derived by a strong symmetric assumption on the conditional correlations. Our derivation clarifies the 'correlation' structure of the beta-binomial distribution. It is also possible to study the correlation structures of other probability distributions of exchangeable (homogeneous) correlated Bernoulli random variables. We study some distribution functions and discuss their behaviours in terms of their correlation structures

Crystal Structure of the HEAT Domain from the Pre-mRNA Processing Factor Symplekin

Energy Technology Data Exchange (ETDEWEB)

Kennedy, Sarah A.; Frazier, Monica L.; Steiniger, Mindy; Mast, Ann M.; Marzluff, William F.; Redinbo, Matthew R.; (UNC)

2010-09-30

The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and polyadenylation, although in metazoa the replication-dependent histone mRNAs are processed by 3'-end cleavage but not polyadenylation. The macromolecular complex responsible for processing both canonical and histone pre-mRNAs contains the {approx} 1160-residue protein Symplekin. Secondary-structural prediction algorithms identified putative HEAT domains in the 300 N-terminal residues of all Symplekins of known sequence. The structure and dynamics of this domain were investigated to begin elucidating the role Symplekin plays in mRNA maturation. The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was determined to 2.4 {angstrom} resolution with single-wavelength anomalous dispersion phasing methods. The structure exhibits five canonical HEAT repeats along with an extended 31-amino-acid loop (loop 8) between the fourth and fifth repeat that is conserved within closely related Symplekin sequences. Molecular dynamics simulations of this domain show that the presence of loop 8 dampens correlated and anticorrelated motion in the HEAT domain, therefore providing a neutral surface for potential protein-protein interactions. HEAT domains are often employed for such macromolecular contacts. The Symplekin HEAT region not only structurally aligns with several established scaffolding proteins, but also has been reported to contact proteins essential for regulating 3'-end processing. Together, these data support the conclusion that the Symplekin HEAT domain serves as a scaffold for protein-protein interactions essential to the mRNA maturation process.

Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design.

Science.gov (United States)

Corradi, Hazel R; Schwager, Sylva L U; Nchinda, Aloysius T; Sturrock, Edward D; Acharya, K Ravi

2006-03-31

Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of "domain-specific" second-generation ACE inhibitors.

Solution structure of leptospiral LigA4 Big domain

Energy Technology Data Exchange (ETDEWEB)

Mei, Song; Zhang, Jiahai [Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhang, Xuecheng [School of Life Sciences, Anhui University, Hefei, Anhui 230039 (China); Tu, Xiaoming, E-mail: xmtu@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China)

2015-11-13

Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca{sup 2+} binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca{sup 2+}-binding site was identified by strains-all and NMR chemical shift perturbation.

Solution structure of leptospiral LigA4 Big domain

International Nuclear Information System (INIS)

Mei, Song; Zhang, Jiahai; Zhang, Xuecheng; Tu, Xiaoming

2015-01-01

Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca"2"+ binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca"2"+-binding site was identified by strains-all and NMR chemical shift perturbation.

On the structure of order domains

DEFF Research Database (Denmark)

Geil, Olav; Pellikaan, Ruud

2002-01-01

The notion of an order domain is generalized. The behaviour of an order domain by taking a subalgebra, the extension of scalars, and the tensor product is studied. The relation of an order domain with valuation theory, Gröbner algebras, and graded structures is given. The theory of Gröbner bases...... for order domains is developed and used to show that the factor ring theorem and its converse, the presentation theorem, hold. The dimension of an order domain is related to the rank of its value semigroup....

LOADS INTERACTION DOMAINS METHODOLOGY FOR THE DESIGN OF STEEL GREENHOUSE STRUCTURES

Directory of Open Access Journals (Sweden)

Sergio Castellano

2007-03-01

Full Text Available Aim of this research is to develop a design methodology which correlates main structural design parameters, whose production is characterised by high levels of standardization, such as the height of gutter or the distance between frames, with actions on the greenhouse. The methodology, based on the use of charts and abacus, permits a clear and a direct interpretation of the structural response to design load combinations and allows the design of structural improvements with the aim of the optimization of the ratio benefits (structural strength/costs. The study of structural interaction domains allowed a clear and a direct interpretation of the structural response to design load combinations. The diagrams highlight not only if the structure fulfils the standard requirements but also the safety levels with respect to design load combinations and allow the structural designer how to operate in order to optimize the structural response with standard requirements achieving the best ratio benefits (structural safety/ costs. The methodology was developed basing on criteria assigned by EN13031 on two different kinds of greenhouse structures: an arched greenhouse with a film plastic covering and a duo pitched roof greenhouse cover with rigid plastic membranes. Structural interaction domains for arched greenhouse showed a better capability of the structure to resist to vertical loads then to horizontal one. Moreover, the climatic load distribution on the structure assigned by EN13031 is such that the combination of climatic actions is less dangerous for the structure then their individual application. Whilst, duo pitched roof steel greenhouse interaction domains, showed a better capability of the structure to resist to vertical loads then to horizontal one and that, in any case, the serviceability limit states analysis is more strict then the ULS one. The shape of structural domains highlighted that the combination of actions is more dangerous for the

Angular correlations of photons from solution diffraction at a free-electron laser encode molecular structure

International Nuclear Information System (INIS)

Mendez, Derek; Watkins, Herschel; Qiao, Shenglan; Raines, Kevin S.; Lane, Thomas J.

2016-01-01

During X-ray exposure of a molecular solution, photons scattered from the same molecule are correlated. If molecular motion is insignificant during exposure, then differences in momentum transfer between correlated photons are direct measurements of the molecular structure. In conventional small- and wide-angle solution scattering, photon correlations are ignored. This report presents advances in a new biomolecular structural analysis technique, correlated X-ray scattering (CXS), which uses angular intensity correlations to recover hidden structural details from molecules in solution. Due to its intense rapid pulses, an X-ray free electron laser (XFEL) is an excellent tool for CXS experiments. A protocol is outlined for analysis of a CXS data set comprising a total of half a million X-ray exposures of solutions of small gold nanoparticles recorded at the Spring-8 Ångström Compact XFEL facility (SACLA). From the scattered intensities and their correlations, two populations of nanoparticle domains within the solution are distinguished: small twinned, and large probably non-twinned domains. Finally, it is shown analytically how, in a solution measurement, twinning information is only accessible via intensity correlations, demonstrating how CXS reveals atomic-level information from a disordered solution of like molecules.

Comparative structural analysis of lipid binding START domains.

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Ann-Gerd Thorsell

Full Text Available Steroidogenic acute regulatory (StAR protein related lipid transfer (START domains are small globular modules that form a cavity where lipids and lipid hormones bind. These domains can transport ligands to facilitate lipid exchange between biological membranes, and they have been postulated to modulate the activity of other domains of the protein in response to ligand binding. More than a dozen human genes encode START domains, and several of them are implicated in a disease.We report crystal structures of the human STARD1, STARD5, STARD13 and STARD14 lipid transfer domains. These represent four of the six functional classes of START domains.Sequence alignments based on these and previously reported crystal structures define the structural determinants of human START domains, both those related to structural framework and those involved in ligand specificity.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

Structure of an isolated unglycosylated antibody CH2 domain

International Nuclear Information System (INIS)

Prabakaran, Ponraj; Vu, Bang K.; Gan, Jianhua; Feng, Yang; Dimitrov, Dimiter S.; Ji, Xinhua

2008-01-01

The crystal structure of an isolated unglycosylated antibody C H 2 domain has been determined at 1.7 Å resolution. The C H 2 (C H 3 for IgM and IgE) domain of an antibody plays an important role in mediating effector functions and preserving antibody stability. It is the only domain in human immunoglobulins (Igs) which is involved in weak interchain protein–protein interactions with another C H 2 domain solely through sugar moieties. The N-linked glycosylation at Asn297 is conserved in mammalian IgGs as well as in homologous regions of other antibody isotypes. To examine the structural details of the C H 2 domain in the absence of glycosylation and other antibody domains, the crystal structure of an isolated unglycosylated antibody γ1 C H 2 domain was determined at 1.7 Å resolution and compared with corresponding C H 2 structures from intact Fc, IgG and Fc receptor complexes. Furthermore, the oligomeric state of the protein in solution was studied using size-exclusion chromatography. The results suggested that the unglycosylated human antibody C H 2 domain is a monomer and that its structure is similar to that found in the intact Fc, IgG and Fc receptor complex structures. However, certain structural variations were observed in the Fc receptor-binding sites. Owing to its small size, stability and non-immunogenic Ig template, the C H 2-domain structure could be useful for the development by protein design of antibody domains exerting effector functions and/or antigen specificity and as a robust scaffold in protein-engineering applications

White matter correlates of cognitive domains in normal aging with diffusion tensor imaging

Directory of Open Access Journals (Sweden)

Efrat eSasson

2013-03-01

Full Text Available The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them. Different cognitive tasks employ distinctive white matter fiber bundles. The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging. In a cohort of 52 healthy subjects (ages 25-82 years, we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory with white matter integrity, as measured by diffusion tensor imaging (DTI fiber tracking in the temporal lobe projections (uncinate fasciculus (UF, fornix, cingulum, inferior longitudinal fasciculus (ILF, and superior longitudinal fasciculus (SLF. The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations. Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF. These findings suggest that DTI tractography enables anatomical definition of region of interest for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity.

Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange: THERMODYNAMIC STABILITY CORRELATES WITH RATES OF UNFOLDING RATHER THAN FOLDING.

Science.gov (United States)

Shah, Riddhi; Ohashi, Tomoo; Erickson, Harold P; Oas, Terrence G

2017-01-20

Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. FNIII domains are one of the most common protein folds and are present in 2% of animal proteins. FNIII domains are ideal for this study because they have an identical seven-strand β-sandwich structure, but they vary widely in sequence and thermodynamic stability. We assayed thermodynamic stability of each domain by equilibrium denaturation in urea. We then assayed the kinetics of domain opening and closing by a technique known as thiol exchange. For this we introduced a buried Cys at the identical location in each FNIII domain and measured the kinetics of labeling with DTNB over a range of urea concentrations. A global fit of the kinetics data gave the kinetics of spontaneous unfolding and refolding in zero urea. We found that the folding rates were relatively similar, ∼0.1-1 s -1 , for the different domains. The unfolding rates varied widely and correlated with thermodynamic stability. Our study is the first to address this question using a set of domains that are structurally homologous but evolved with widely varying sequence identity and thermodynamic stability. These data add new evidence that thermodynamic stability correlates primarily with unfolding rate rather than folding rate. The study also has implications for the question of whether opening of FNIII domains contributes to the stretching of fibronectin matrix fibrils. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Stationary echo canceling in velocity estimation by time-domain cross-correlation

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt

1993-01-01

The application of stationary echo canceling to ultrasonic estimation of blood velocities using time-domain cross-correlation is investigated. Expressions are derived that show the influence from the echo canceler on the signals that enter the cross-correlation estimator. It is demonstrated...

An Algebro-Topological Description of Protein Domain Structure

Science.gov (United States)

Penner, Robert Clark; Knudsen, Michael; Wiuf, Carsten; Andersen, Jørgen Ellegaard

2011-01-01

The space of possible protein structures appears vast and continuous, and the relationship between primary, secondary and tertiary structure levels is complex. Protein structure comparison and classification is therefore a difficult but important task since structure is a determinant for molecular interaction and function. We introduce a novel mathematical abstraction based on geometric topology to describe protein domain structure. Using the locations of the backbone atoms and the hydrogen bonds, we build a combinatorial object – a so-called fatgraph. The description is discrete yet gives rise to a 2-dimensional mathematical surface. Thus, each protein domain corresponds to a particular mathematical surface with characteristic topological invariants, such as the genus (number of holes) and the number of boundary components. Both invariants are global fatgraph features reflecting the interconnectivity of the domain by hydrogen bonds. We introduce the notion of robust variables, that is variables that are robust towards minor changes in the structure/fatgraph, and show that the genus and the number of boundary components are robust. Further, we invesigate the distribution of different fatgraph variables and show how only four variables are capable of distinguishing different folds. We use local (secondary) and global (tertiary) fatgraph features to describe domain structures and illustrate that they are useful for classification of domains in CATH. In addition, we combine our method with two other methods thereby using primary, secondary, and tertiary structure information, and show that we can identify a large percentage of new and unclassified structures in CATH. PMID:21629687

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

Science.gov (United States)

Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

2018-02-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

Structure and dynamics of the human pleckstrin DEP domain: distinct molecular features of a novel DEP domain subfamily.

Science.gov (United States)

Civera, Concepcion; Simon, Bernd; Stier, Gunter; Sattler, Michael; Macias, Maria J

2005-02-01

Pleckstrin1 is a major substrate for protein kinase C in platelets and leukocytes, and comprises a central DEP (disheveled, Egl-10, pleckstrin) domain, which is flanked by two PH (pleckstrin homology) domains. DEP domains display a unique alpha/beta fold and have been implicated in membrane binding utilizing different mechanisms. Using multiple sequence alignments and phylogenetic tree reconstructions, we find that 6 subfamilies of the DEP domain exist, of which pleckstrin represents a novel and distinct subfamily. To clarify structural determinants of the DEP fold and to gain further insight into the role of the DEP domain, we determined the three-dimensional structure of the pleckstrin DEP domain using heteronuclear NMR spectroscopy. Pleckstrin DEP shares main structural features with the DEP domains of disheveled and Epac, which belong to different DEP subfamilies. However, the pleckstrin DEP fold is distinct from these structures and contains an additional, short helix alpha4 inserted in the beta4-beta5 loop that exhibits increased backbone mobility as judged by NMR relaxation measurements. Based on sequence conservation, the helix alpha4 may also be present in the DEP domains of regulator of G-protein signaling (RGS) proteins, which are members of the same DEP subfamily. In pleckstrin, the DEP domain is surrounded by two PH domains. Structural analysis and charge complementarity suggest that the DEP domain may interact with the N-terminal PH domain in pleckstrin. Phosphorylation of the PH-DEP linker, which is required for pleckstrin function, could regulate such an intramolecular interaction. This suggests a role of the pleckstrin DEP domain in intramolecular domain interactions, which is distinct from the functions of other DEP domain subfamilies found so far.

Structure of synaptophysin: a hexameric MARVEL-domain channel protein.

Science.gov (United States)

Arthur, Christopher P; Stowell, Michael H B

2007-06-01

Synaptophysin I (SypI) is an archetypal member of the MARVEL-domain family of integral membrane proteins and one of the first synaptic vesicle proteins to be identified and cloned. Most all MARVEL-domain proteins are involved in membrane apposition and vesicle-trafficking events, but their precise role in these processes is unclear. We have purified mammalian SypI and determined its three-dimensional (3D) structure by using electron microscopy and single-particle 3D reconstruction. The hexameric structure resembles an open basket with a large pore and tenuous interactions within the cytosolic domain. The structure suggests a model for Synaptophysin's role in fusion and recycling that is regulated by known interactions with the SNARE machinery. This 3D structure of a MARVEL-domain protein provides a structural foundation for understanding the role of these important proteins in a variety of biological processes.

Structural and Histone Binding Ability Characterizations of Human PWWP Domains

Energy Technology Data Exchange (ETDEWEB)

Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Amaya, Maria F.; Xu, Chao; Dombrovski, Ludmila; Qiu, Wei; Wang, Yanming; Min, Jinrong (Toronto); (Penn)

2013-09-25

The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.

Identification of structural domains in proteins by a graph heuristic

NARCIS (Netherlands)

Wernisch, Lorenz; Hunting, M.M.G.; Wodak, Shoshana J.

1999-01-01

A novel automatic procedure for identifying domains from protein atomic coordinates is presented. The procedure, termed STRUDL (STRUctural Domain Limits), does not take into account information on secondary structures and handles any number of domains made up of contiguous or non-contiguous chain

Solution structure of the isolated Pelle death domain.

Science.gov (United States)

Moncrieffe, Martin C; Stott, Katherine M; Gay, Nicholas J

2005-07-18

The interaction between the death domains (DDs) of Tube and the protein kinase Pelle is an important component of the Toll pathway. Published crystallographic data suggests that the Pelle-Tube DD interface is plastic and implies that in addition to the two predominant Pelle-Tube interfaces, a third interaction is possible. We present the NMR solution structure of the isolated death domain of Pelle and a study of the interaction between the DDs of Pelle and Tube. Our data suggests the solution structure of the isolated Pelle DD is similar to that of Pelle DD in complex with Tube. Additionally, they suggest that the plasticity observed in the crystal structure may not be relevant in the functioning death domain complex.

Explaining the Substantial Inter-Domain and Over-Time Correlations in Student Achievement: The Importance of Stable Student Attributes

Science.gov (United States)

Marks, Gary N.

2016-01-01

Multi-domain and longitudinal studies of student achievement routinely find moderate to strong correlations across achievement domains and even stronger within-domain correlations over time. The purpose of this study is to examine the sources of these patterns analysing student achievement in 5 domains across Years 3, 5 and 7. The analysis is of…

Identifying secondary structures in proteins using NMR chemical shift 3D correlation maps

Science.gov (United States)

Kumari, Amrita; Dorai, Kavita

2013-06-01

NMR chemical shifts are accurate indicators of molecular environment and have been extensively used as aids in protein structure determination. This work focuses on creating empirical 3D correlation maps of backbone chemical shift nuclei for use as identifiers of secondary structure elements in proteins. A correlated database of backbone nuclei chemical shifts was constructed from experimental structural data gathered from entries in the Protein Data Bank (PDB) as well as isotropic chemical shift values from the RefDB database. Rigorous statistical analysis of the maps led to the conclusion that specific correlations between triplets of backbone chemical shifts are best able to differentiate between different secondary structures such as α-helices, β-strands and turns. The method is compared with similar techniques that use NMR chemical shift information as aids in biomolecular structure determination and performs well in tests done on experimental data determined for different types of proteins, including large multi-domain proteins and membrane proteins.

Mapping the structural and dynamical features of kinesin motor domains.

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Guido Scarabelli

Full Text Available Kinesin motor proteins drive intracellular transport by coupling ATP hydrolysis to conformational changes that mediate directed movement along microtubules. Characterizing these distinct conformations and their interconversion mechanism is essential to determining an atomic-level model of kinesin action. Here we report a comprehensive principal component analysis of 114 experimental structures along with the results of conventional and accelerated molecular dynamics simulations that together map the structural dynamics of the kinesin motor domain. All experimental structures were found to reside in one of three distinct conformational clusters (ATP-like, ADP-like and Eg5 inhibitor-bound. These groups differ in the orientation of key functional elements, most notably the microtubule binding α4-α5, loop8 subdomain and α2b-β4-β6-β7 motor domain tip. Group membership was found not to correlate with the nature of the bound nucleotide in a given structure. However, groupings were coincident with distinct neck-linker orientations. Accelerated molecular dynamics simulations of ATP, ADP and nucleotide free Eg5 indicate that all three nucleotide states could sample the major crystallographically observed conformations. Differences in the dynamic coupling of distal sites were also evident. In multiple ATP bound simulations, the neck-linker, loop8 and the α4-α5 subdomain display correlated motions that are absent in ADP bound simulations. Further dissection of these couplings provides evidence for a network of dynamic communication between the active site, microtubule-binding interface and neck-linker via loop7 and loop13. Additional simulations indicate that the mutations G325A and G326A in loop13 reduce the flexibility of these regions and disrupt their couplings. Our combined results indicate that the reported ATP and ADP-like conformations of kinesin are intrinsically accessible regardless of nucleotide state and support a model where neck

Theoretical Methods of Domain Structures in Ultrathin Ferroelectric Films: A Review

Directory of Open Access Journals (Sweden)

Jianyi Liu

2014-09-01

Full Text Available This review covers methods and recent developments of the theoretical study of domain structures in ultrathin ferroelectric films. The review begins with an introduction to some basic concepts and theories (e.g., polarization and its modern theory, ferroelectric phase transition, domain formation, and finite size effects, etc. that are relevant to the study of domain structures in ultrathin ferroelectric films. Basic techniques and recent progress of a variety of important approaches for domain structure simulation, including first-principles calculation, molecular dynamics, Monte Carlo simulation, effective Hamiltonian approach and phase field modeling, as well as multiscale simulation are then elaborated. For each approach, its important features and relative merits over other approaches for modeling domain structures in ultrathin ferroelectric films are discussed. Finally, we review recent theoretical studies on some important issues of domain structures in ultrathin ferroelectric films, with an emphasis on the effects of interfacial electrostatics, boundary conditions and external loads.

Crystal structure of the Ig1 domain of the neural cell adhesion molecule NCAM2 displays domain swapping

DEFF Research Database (Denmark)

Rasmussen, Kim Krighaar; Kulahin, Nikolaj; Kristensen, Ole

2008-01-01

The crystal structure of the first immunoglobulin (Ig1) domain of neural cell adhesion molecule 2 (NCAM2/OCAM/RNCAM) is presented at a resolution of 2.7 A. NCAM2 is a member of the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). In the structure, two Ig domains interact by domain...

Chirality correlation within Dirac eigenvectors from domain wall fermions

International Nuclear Information System (INIS)

Blum, T.; Christ, N.; Cristian, C.; Liao, X.; Liu, G.; Mawhinney, R.; Wu, L.; Zhestkov, Y.; Dawson, C.

2002-01-01

In the dilute instanton gas model of the QCD vacuum, one expects a strong spatial correlation between chirality and the maxima of the Dirac eigenvectors with small eigenvalues. Following Horvath et al. we examine this question using lattice gauge theory within the quenched approximation. We extend the work of those authors by using weaker coupling, β=6.0, larger lattices, 16 4 , and an improved fermion formulation, domain wall fermions. In contrast with this earlier work, we find a striking correlation between the magnitudes of the chirality density, |ψ † (x)γ 5 ψ(x)|, and the normal density, ψ † (x)ψ(x), for the low-lying Dirac eigenvectors

Photoinduced domain structures in monocrystalline films of yttrium-iron garnets

International Nuclear Information System (INIS)

Doroshenko, R.A.; Vladimirov, I.V.; Setchenkov, M.S.

1988-01-01

Results of investigating the domain structure in Y 3 Fe 5 O 12 epitaxial films under polarized light effect are presented. The domain structure was observed using Faraday effect at 80 K, crystallographic directions were determined by X-ray method. The sample structure is shown to consist of macrodomains, which parallel boundaries are oriented on (011), (110), (101) and are reoriented under the light effect, therewith easiest magnetization axes are brought about perpendicular to vector E of the affecting light. When explaining such changes in domain structure elastic stresses and induced anisotropy of elastic nature must be taken accout of

Local mobility in lipid domains of supported bilayers characterized by atomic force microscopy and fluorescence correlation spectroscopy.

Energy Technology Data Exchange (ETDEWEB)

Frankel, Daniel J.; Buranda, T. (University of New Mexico, Albuquerque, NM); Burns, Alan Richard

2005-01-01

Fluorescence correlation spectroscopy (FCS) is used to examine mobility of labeled probes at specific sites in supported bilayers consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid domains in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). Those sites are mapped beforehand with simultaneous atomic force microscopy and submicron confocal fluorescence imaging, allowing characterization of probe partitioning between gel DPPC and disordered liquid DOPC domains with corresponding topography of domain structure. We thus examine the relative partitioning and mobility in gel and disordered liquid phases for headgroup- and tailgroup-labeled GM1 ganglioside probes and for headgroup- and tailgroup-labeled phospholipid probes. For the GM1 probes, large differences in mobility between fluid and gel domains are observed; whereas unexpected mobility is observed in submicron gel domains for the phospholipid probes. We attribute the latter to domain heterogeneities that could be induced by the probe. Furthermore, fits to the FCS data for the phospholipid probes in the DOPC fluid phase require two components (fast and slow). Although proximity to the glass substrate may be a factor, local distortion of the probe by the fluorophore could also be important. Overall, we observe nonideal aspects of phospholipid probe mobility and partitioning that may not be restricted to supported bilayers.

Magnetic domain structure in a metamagnetic shape memory alloy Ni45Co5Mn36.7In13.3

International Nuclear Information System (INIS)

Murakami, Y.; Yano, T.; Shindo, D.; Kainuma, R.; Oikawa, K.; Ishida, K.

2006-01-01

Correlation between the magnetism and the martensitic transformation in Ni 45 Co 5 Mn 36.7 In 13.3 has been revealed by electron holography and Lorentz microscopy. The parent phase exhibits typical closure magnetic domains due to low magnetocrystalline anisotropy. Upon cooling, the magnetic flux density of the parent phase monotonically increases, while the magnetic domain structure remains almost unchanged; in other words, the effect of premartensitic lattice modulation appears to be small in this alloy. The magnetic domains disappear immediately when the martensitic transformation occurs

Structure of the thioredoxin-fold domain of human phosducin-like protein 2

International Nuclear Information System (INIS)

Lou, Xiaochu; Bao, Rui; Zhou, Cong-Zhao; Chen, Yuxing

2009-01-01

The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Human phosducin-like protein 2 (hPDCL2) has been identified as belonging to subgroup II of the phosducin (Pdc) family. The members of this family share an N-terminal helix domain and a C-terminal thioredoxin-fold (Trx-fold) domain. The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Comparative structural analysis revealed the structural basis of their putative functional divergence

Structural and magnetic domains characterization of magnetite nanoparticles

International Nuclear Information System (INIS)

Santoyo-Salazar, J.; Castellanos-Roman, M.A.; Beatriz Gomez, L.

2007-01-01

Recently, important advances have been achieved in application, reproducibility and response ability of magnetic materials due to the relationships among processing, structure and nanometric size particle. Features like homogeneity of compounds and nanoparticle-sizing have improved some magnetic properties of materials and their field application. Of particular interest is the study of magnetic materials at the atomic and microstuctural level because the orientation and magnetic domains (large numbers of atoms moments coupled together in a preferential direction) can be observed. In this work, magnetite (Fe 3 O 4 ) powders which were obtained by precipitation route in alkaline medium are analyzed to identify the structure and mechanism formation of domains over the core and border of nanoparticles. Results obtained by XRD, atomic force microscopy (AFM) and magnetic force microscopy (MFM) showed a structural phase corresponding to Fe 3 O 4 and nanoparticles in a range of 20-40 nm. Samples scanned by MFM in nanometric resolution and profile images showed orientation of magnetic domains in the border and cores of the material. Finally, an analysis of repulsion and attraction in magnetic field and direction changes of domains formed by magnetite (Fe 3 O 4 ) powders were done

Structural and functional analysis of multi-interface domains.

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Liang Zhao

Full Text Available A multi-interface domain is a domain that can shape multiple and distinctive binding sites to contact with many other domains, forming a hub in domain-domain interaction networks. The functions played by the multiple interfaces are usually different, but there is no strict bijection between the functions and interfaces as some subsets of the interfaces play the same function. This work applies graph theory and algorithms to discover fingerprints for the multiple interfaces of a domain and to establish associations between the interfaces and functions, based on a huge set of multi-interface proteins from PDB. We found that about 40% of proteins have the multi-interface property, however the involved multi-interface domains account for only a tiny fraction (1.8% of the total number of domains. The interfaces of these domains are distinguishable in terms of their fingerprints, indicating the functional specificity of the multiple interfaces in a domain. Furthermore, we observed that both cooperative and distinctive structural patterns, which will be useful for protein engineering, exist in the multiple interfaces of a domain.

Structure correlation and chemistry

International Nuclear Information System (INIS)

Buergi, H.B.

1998-01-01

The main goal of crystal and molecular structure determination is to provide a starting point for understanding the physical, chemical and biological properties of matter. At present, results from nearly 300000 crystal structure studies are available in computer-readable form. Structure correlation attempts to extract knowledge and understanding from this body of information, which is not available from its parts. This article reviews some typical examples: libraries of prototypal molecular dimensions, mappings of chemical reaction pathways, correlations between structure on one hand and energy, reaction rate, catalytic activity or magnetism on the other. The knowledge gained from structure-correlation studies, together with quantum-chemical and other modeling techniques, provides conceptual and practical tools for designing molecules and materials with tailor-made properties. (orig.)

A Novel Sub-pixel Measurement Algorithm Based on Mixed the Fractal and Digital Speckle Correlation in Frequency Domain

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Zhangfang Hu

2014-10-01

Full Text Available The digital speckle correlation is a non-contact in-plane displacement measurement method based on machine vision. Motivated by the facts that the low accuracy and large amount of calculation produced by the traditional digital speckle correlation method in spatial domain, we introduce a sub-pixel displacement measurement algorithm which employs a fast interpolation method based on fractal theory and digital speckle correlation in frequency domain. This algorithm can overcome either the blocking effect or the blurring caused by the traditional interpolation methods, and the frequency domain processing also avoids the repeated searching in the correlation recognition of the spatial domain, thus the operation quantity is largely reduced and the information extracting speed is improved. The comparative experiment is given to verify that the proposed algorithm in this paper is effective.

Cross-domain correlation in pitch perception, the influence of native language

NARCIS (Netherlands)

Chen, A.; Liu, L.; Kager, R.W.J.

2016-01-01

The current study explores how language experience may shape the correlation between lexical tone and musical pitch perception. A two domains (music and lexical tone) by two languages (tone, Mandarin Chinese and non-tone, Dutch) design is adopted. Participants were tested on their discrimination of

Mapping small molecule binding data to structural domains.

Science.gov (United States)

Kruger, Felix A; Rostom, Raghd; Overington, John P

2012-01-01

Large-scale bioactivity/SAR Open Data has recently become available, and this has allowed new analyses and approaches to be developed to help address the productivity and translational gaps of current drug discovery. One of the current limitations of these data is the relative sparsity of reported interactions per protein target, and complexities in establishing clear relationships between bioactivity and targets using bioinformatics tools. We detail in this paper the indexing of targets by the structural domains that bind (or are likely to bind) the ligand within a full-length protein. Specifically, we present a simple heuristic to map small molecule binding to Pfam domains. This profiling can be applied to all proteins within a genome to give some indications of the potential pharmacological modulation and regulation of all proteins. In this implementation of our heuristic, ligand binding to protein targets from the ChEMBL database was mapped to structural domains as defined by profiles contained within the Pfam-A database. Our mapping suggests that the majority of assay targets within the current version of the ChEMBL database bind ligands through a small number of highly prevalent domains, and conversely the majority of Pfam domains sampled by our data play no currently established role in ligand binding. Validation studies, carried out firstly against Uniprot entries with expert binding-site annotation and secondly against entries in the wwPDB repository of crystallographic protein structures, demonstrate that our simple heuristic maps ligand binding to the correct domain in about 90 percent of all assessed cases. Using the mappings obtained with our heuristic, we have assembled ligand sets associated with each Pfam domain. Small molecule binding has been mapped to Pfam-A domains of protein targets in the ChEMBL bioactivity database. The result of this mapping is an enriched annotation of small molecule bioactivity data and a grouping of activity classes

Structure of the interleukin-2 tyrosine kinase Src homology 2 domain; comparison between X-ray and NMR-derived structures

International Nuclear Information System (INIS)

Joseph, Raji E.; Ginder, Nathaniel D.; Hoy, Julie A.; Nix, Jay C.; Fulton, D. Bruce; Honzatko, Richard B.; Andreotti, Amy H.

2012-01-01

The interleukin-2 tyrosine kinase Src homology 2 domain was crystallized and its structure was solved to 2.35 Å resolution. The structure reveals a domain-swapped dimer that is related to other dimeric SH2 domains solved previously. The cis–trans-prolyl isomerization that is evident from solution studies of Itk SH2 cannot be observed in the crystal structure. The crystal structure of the interleukin-2 tyrosine kinase Src homology domain (Itk SH2) is described and it is found that unlike in studies of this domain using NMR spectroscopy, cis–trans-prolyl isomerization is not readily detected in the crystal structure. Based on similarities between the Itk SH2 crystal form and the cis form of the Itk SH2 NMR structure, it is concluded that it is likely that the prolyl imide bond at least in part adopts the cis conformation in the crystal form. However, the lack of high-resolution data and the dynamic nature of the proline-containing loop mean that the precise imide-bond conformation cannot be determined and prolyl cis–trans isomerization in the crystal cannot be ruled out. Given the preponderance of structures that have been solved by X-ray crystallography in the Protein Data Bank, this result supports the notion that prolyl isomerization in folded proteins has been underestimated among known structures. Interestingly, while the precise status of the proline residue is ambiguous, Itk SH2 crystallizes as a domain-swapped dimer. The domain-swapped structure of Itk SH2 is similar to the domain-swapped SH2 domains of Grb2 and Nck, with domain swapping occurring at the β-meander region of all three SH2 domains. Thus, for Itk SH2 structural analysis by NMR spectroscopy and X-ray crystallography revealed very different structural features: proline isomerization versus domain-swapped dimerization, respectively

Using Common Spatial Distributions of Atoms to Relate Functionally Divergent Influenza Virus N10 and N11 Protein Structures to Functionally Characterized Neuraminidase Structures, Toxin Cell Entry Domains, and Non-Influenza Virus Cell Entry Domains

Science.gov (United States)

Weininger, Arthur; Weininger, Susan

2015-01-01

The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell

Corrections for frequency domain transformations of Winfrith binary cross correlator responses

International Nuclear Information System (INIS)

Cummins, J.D.

1968-04-01

This report considers the corrections for frequency domain transformations of Winfrith binary cross correlator responses; (i) for the finite bandwidth of the equivalent input signal; (2) for the finite time required for the actuator to move between the two positions appropriate to the two levels of the periodic binary chain code input and (3) for the averaging of experimental determinations of the system frequency response and calculations of the standard deviations of the modulus and phase of the frequency responses determined from the cross correlator responses. (author)

Reliability analysis based on a novel density estimation method for structures with correlations

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Baoyu LI

2017-06-01

Full Text Available Estimating the Probability Density Function (PDF of the performance function is a direct way for structural reliability analysis, and the failure probability can be easily obtained by integration in the failure domain. However, efficiently estimating the PDF is still an urgent problem to be solved. The existing fractional moment based maximum entropy has provided a very advanced method for the PDF estimation, whereas the main shortcoming is that it limits the application of the reliability analysis method only to structures with independent inputs. While in fact, structures with correlated inputs always exist in engineering, thus this paper improves the maximum entropy method, and applies the Unscented Transformation (UT technique to compute the fractional moments of the performance function for structures with correlations, which is a very efficient moment estimation method for models with any inputs. The proposed method can precisely estimate the probability distributions of performance functions for structures with correlations. Besides, the number of function evaluations of the proposed method in reliability analysis, which is determined by UT, is really small. Several examples are employed to illustrate the accuracy and advantages of the proposed method.

Structural Basis for Endosomal Targeting by the Bro1 Domain

Science.gov (United States)

Kim, Jaewon; Sitaraman, Sujatha; Hierro, Aitor; Beach, Bridgette M.; Odorizzi, Greg; Hurley, James H.

2010-01-01

Summary Proteins delivered to the lysosome or the yeast vacuole via late endosomes are sorted by the ESCRT complexes and by associated proteins, including Alix and its yeast homolog Bro1. Alix, Bro1, and several other late endosomal proteins share a conserved 160 residue Bro1 domain whose boundaries, structure, and function have not been characterized. The crystal structure of the Bro1 domain of Bro1 reveals a folded core of 367 residues. The extended Bro1 domain is necessary and sufficient for binding to the ESCRT-III subunit Snf7 and for the recruitment of Bro1 to late endosomes. The structure resembles a boomerang with its concave face filled in and contains a triple tetratricopeptide repeat domain as a substructure. Snf7 binds to a conserved hydrophobic patch on Bro1 that is required for protein complex formation and for the protein-sorting function of Bro1. These results define a conserved mechanism whereby Bro1 domain-containing proteins are targeted to endosomes by Snf7 and its orthologs. PMID:15935782

Eliminating the domain error in local explicitly correlated second-order Møller-Plesset perturbation theory.

Science.gov (United States)

Werner, Hans-Joachim

2008-09-14

A new explicitly correlated local MP2-F12 method is proposed in which the error caused by truncating the virtual orbital space to pair-specific local domains is almost entirely removed. This is achieved by a simple modification of the ansatz for the explicitly correlated wave function, which makes it possible that the explicitly correlated terms correct both for the basis set incompleteness error as well as for the domain error in the LMP2. Benchmark calculations are presented for 21 molecules and 16 chemical reactions. The results demonstrate that the local approximations have hardly any effect on the accuracy of the computed correlation energies and reaction energies, and the LMP2-F12 reaction energies agree within 0.1-0.2 kcal/mol with estimated MP2 basis set limits.

Structural basis of antifreeze activity of a bacterial multi-domain antifreeze protein.

Directory of Open Access Journals (Sweden)

Chen Wang

Full Text Available Antifreeze proteins (AFPs enhance the survival of organisms inhabiting cold environments by affecting the formation and/or structure of ice. We report the crystal structure of the first multi-domain AFP that has been characterized. The two ice binding domains are structurally similar. Each consists of an irregular β-helix with a triangular cross-section and a long α-helix that runs parallel on one side of the β-helix. Both domains are stabilized by hydrophobic interactions. A flat plane on the same face of each domain's β-helix was identified as the ice binding site. Mutating any of the smaller residues on the ice binding site to bulkier ones decreased the antifreeze activity. The bulky side chain of Leu174 in domain A sterically hinders the binding of water molecules to the protein backbone, partially explaining why antifreeze activity by domain A is inferior to that of domain B. Our data provide a molecular basis for understanding differences in antifreeze activity between the two domains of this protein and general insight on how structural differences in the ice-binding sites affect the activity of AFPs.

The correlation between the length of repetitive domain and mechanical properties of the recombinant flagelliform spidroin

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Xue Li

2017-03-01

Full Text Available Spider silk is an attractive biopolymer with numerous potential applications due to its remarkable characteristics. Among the six categories of spider silks, flagelliform (Flag spider silk possesses longer and more repetitive core domains than others, therefore performing the highest extensibility. To investigate the correlation between the recombinant spidroin size and the synthetic fiber properties, four recombinant proteins with different sizes [N-Scn-C (n=1-4] were constructed and expressed using IMPACT system. Subsequently, different recombinant spidroins were spun into fibers through wet-spinning via a custom-made continuous post-drawing device. Mechanical tests of the synthetic fibers with four parameters (maximum stress, maximum extension, Young's modulus and toughness demonstrated that the extensibility of the fibers showed a positive correlation with spidroin size, consequently resulting in the extensibility of N-Sc4-C fiber ranked the highest (58.76% among four fibers. Raman data revealed the relationship between secondary structure content and mechanical properties. The data here provide a deeper insight into the relationship between the function and structure of Flag silk for future design of artificial fibers.

Structure-function relationships using spectral-domain optical coherence tomography: comparison with scanning laser polarimetry.

Science.gov (United States)

Aptel, Florent; Sayous, Romain; Fortoul, Vincent; Beccat, Sylvain; Denis, Philippe

2010-12-01

To evaluate and compare the regional relationships between visual field sensitivity and retinal nerve fiber layer (RNFL) thickness as measured by spectral-domain optical coherence tomography (OCT) and scanning laser polarimetry. Prospective cross-sectional study. One hundred and twenty eyes of 120 patients (40 with healthy eyes, 40 with suspected glaucoma, and 40 with glaucoma) were tested on Cirrus-OCT, GDx VCC, and standard automated perimetry. Raw data on RNFL thickness were extracted for 256 peripapillary sectors of 1.40625 degrees each for the OCT measurement ellipse and 64 peripapillary sectors of 5.625 degrees each for the GDx VCC measurement ellipse. Correlations between peripapillary RNFL thickness in 6 sectors and visual field sensitivity in the 6 corresponding areas were evaluated using linear and logarithmic regression analysis. Receiver operating curve areas were calculated for each instrument. With spectral-domain OCT, the correlations (r(2)) between RNFL thickness and visual field sensitivity ranged from 0.082 (nasal RNFL and corresponding visual field area, linear regression) to 0.726 (supratemporal RNFL and corresponding visual field area, logarithmic regression). By comparison, with GDx-VCC, the correlations ranged from 0.062 (temporal RNFL and corresponding visual field area, linear regression) to 0.362 (supratemporal RNFL and corresponding visual field area, logarithmic regression). In pairwise comparisons, these structure-function correlations were generally stronger with spectral-domain OCT than with GDx VCC and with logarithmic regression than with linear regression. The largest areas under the receiver operating curve were seen for OCT superior thickness (0.963 ± 0.022; P polarimetry, and was better expressed logarithmically than linearly. Measurements with these 2 instruments should not be considered to be interchangeable. Copyright © 2010 Elsevier Inc. All rights reserved.

The structure of the nucleoprotein binding domain of lyssavirus phosphoprotein reveals a structural relationship between the N-RNA binding domains of Rhabdoviridae and Paramyxoviridae.

Science.gov (United States)

Delmas, Olivier; Assenberg, Rene; Grimes, Jonathan M; Bourhy, Hervé

2010-01-01

The phosphoprotein P of non-segmented negative-sense RNA viruses is an essential component of the replication and transcription complex and acts as a co-factor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. We have obtained the structure of the C-terminal domain of P of Mokola virus (MOKV), a lyssavirus that belongs to the Rhabdoviridae family and mapped at the amino acid level the crucial positions involved in interaction with N and in the formation of the viral replication complex. Comparison of the N-RNA binding domains of P solved to date suggests that the N-RNA binding domains are structurally conserved among paramyxoviruses and rhabdoviruses in spite of low sequence conservation. We also review the numerous other functions of this domain and more generally of the phosphoprotein.

Effects of sub-domain structure on initial magnetization curve and domain size distribution of stacked media

International Nuclear Information System (INIS)

Sato, S.; Kumagai, S.; Sugita, R.

2015-01-01

In this paper, in order to confirm the sub-domain structure in stacked media demagnetized with in-plane field, initial magnetization curves and magnetic domain size distribution were investigated. Both experimental and simulation results showed that an initial magnetization curve for the medium demagnetized with in-plane field (MDI) initially rose faster than that for the medium demagnetized with perpendicular field (MDP). It is inferred that this is because the MDI has a larger number of domain walls than the MDP due to the existence of the sub-domains, resulting in an increase in the probability of domain wall motion. Dispersion of domain size for the MDI was larger than that for the MDP. This is because sub-domains are formed not only inside the domain but also at the domain boundary region, and they change the position of the domain boundary to affect the domain size. - Highlights: • An initial magnetization curve for MDI initially rose faster than that for MDP. • Dispersion of domain size for the MDI was larger than that for the MDP. • Experimental and simulation results can be explained by existence of sub-domains

A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

Science.gov (United States)

Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

2014-06-01

Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

DIMA 3.0: Domain Interaction Map.

Science.gov (United States)

Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij

2011-01-01

Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.

Correlation Structures of Correlated Binomial Models and Implied Default Distribution

Science.gov (United States)

Mori, Shintaro; Kitsukawa, Kenji; Hisakado, Masato

2008-11-01

We show how to analyze and interpret the correlation structures, the conditional expectation values and correlation coefficients of exchangeable Bernoulli random variables. We study implied default distributions for the iTraxx-CJ tranches and some popular probabilistic models, including the Gaussian copula model, Beta binomial distribution model and long-range Ising model. We interpret the differences in their profiles in terms of the correlation structures. The implied default distribution has singular correlation structures, reflecting the credit market implications. We point out two possible origins of the singular behavior.

Anti-phase boundaries and magnetic domain structures in Ni{sub 2}MnGa-type Heusler alloys

Energy Technology Data Exchange (ETDEWEB)

Venkateswaran, S.P. [Department of Materials Science and Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213 (United States); Nuhfer, N.T. [Department of Materials Science and Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213 (United States); De Graef, M. [Department of Materials Science and Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213 (United States)]. E-mail: degraef@cmu.edu

2007-05-15

The microstructure and magnetic domain structure of austenitic Heusler Ni{sub 2}MnGa are investigated as a function of heat treatment to study the interplay of anti-phase boundaries and magnetic domain walls. Conventional electron microscopy observations on arc-melted polycrystalline samples show that anti-phase boundaries in this system are invisible for standard two-beam imaging conditions, due to the large extinction distance of the Heusler superlattice reflections. Lorentz Fresnel and Foucault observations on quenched samples reveal a wavy magnetic domain morphology, reminiscent of curved anti-phase boundaries. A close inspection of the domain images indicates that the anti-phase boundaries have a magnetization state different from that of the matrix. Fresnel image simulations for a simple magnetization model are in good agreement with the observations. Magnetic coercivity measurements show a decrease in coercivity with annealing, which correlates with the microscopy observations of reduced anti-phase boundary density for annealed samples.

Magnetic and topographic correlations in Co nanoparticles

International Nuclear Information System (INIS)

Ciria, M.; Arnaudas, J.I.; Huttel, Y.; Gomez, H.; Cebollada, A.; Armelles, G.

2007-01-01

We present a study of the magnetic domains structure in Co films grown on AlN composed of particles with nominal thicknesses between 3 and 15 nm. The images taken by using a scanning force microscope show that as the film thickness increases the domains have the magnetization vector pointing out of the plane, and that the magnetization in the particle tends to be in a single domain state with the particle boundaries being the main source for domains boundaries. The variation of the magnetic and topographic correlation functions in terms of the particle thickness suggests that the magnetic state is formed by a correlated super-spin glass structure

Threading structural model of the manganese-stabilizing protein PsbO reveals presence of two possible beta-sandwich domains.

Science.gov (United States)

Pazos, F; Heredia, P; Valencia, A; de las Rivas, J

2001-12-01

The manganese-stabilizing protein (PsbO) is an essential component of photosystem II (PSII) and is present in all oxyphotosynthetic organisms. PsbO allows correct water splitting and oxygen evolution by stabilizing the reactions driven by the manganese cluster. Despite its important role, its structure and detailed functional mechanism are still unknown. In this article we propose a structural model based on fold recognition and molecular modeling. This model has additional support from a study of the distribution of characteristics of the PsbO sequence family, such as the distribution of conserved, apolar, tree-determinants, and correlated positions. Our threading results consistently showed PsbO as an all-beta (beta) protein, with two homologous beta domains of approximately 120 amino acids linked by a flexible Proline-Glycine-Glycine (PGG) motif. These features are compatible with a general elongated and flexible architecture, in which the two domains form a sandwich-type structure with Greek key topology. The first domain is predicted to include 8 to 9 beta-strands, the second domain 6 to 7 beta-strands. An Ig-like beta-sandwich structure was selected as a template to build the 3-D model. The second domain has, between the strands, long-loops rich in Pro and Gly that are difficult to model. One of these long loops includes a highly conserved region (between P148 and P174) and a short alpha-helix (between E181 and N188)). These regions are characteristic parts of PsbO and show that the second domain is not so similar to the template. Overall, the model was able to account for much of the experimental data reported by several authors, and it would allow the detection of key residues and regions that are proposed in this article as essential for the structure and function of PsbO. Copyright 2001 Wiley-Liss, Inc.

Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

Science.gov (United States)

Dong, Zheng; Zhou, Hongyu; Tao, Peng

2018-02-01

PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

Domain Structures in Nematic Liquid Crystals on a Polycarbonate Surface

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Vasily F. Shabanov

2013-08-01

Full Text Available Alignment of nematic liquid crystals on polycarbonate films obtained with the use of solvents with different solvations is studied. Domain structures occurring during the growth on the polymer surface against the background of the initial thread-like or schlieren texture are demonstrated. It is established by optical methods that the domains are stable formations visualizing the polymer surface structures. In nematic droplets, the temperature-induced transition from the domain structure with two extinction bands to the structure with four bands is observed. This transition is shown to be caused by reorientation of the nematic director in the liquid crystal volume from the planar alignment to the homeotropic state with the pronounced radial configuration of nematic molecules on the surface. The observed textures are compared with different combinations of the volume LC orientations and the radial distribution of the director field and the disclination lines at the polycarbonate surface.

Perceived correlates of domain-specific physical activity in rural adults in the Midwest.

Science.gov (United States)

Chrisman, Matthew; Nothwehr, Faryle; Yang, Jingzen; Oleson, Jacob

2014-01-01

In response to calls for more specificity when measuring physical activity, this study examined perceived correlates of this behavior in rural adults separately by the domain in which this behavior occurs (ie, home care, work, active living, and sport). A cross-sectional survey was completed by 407 adults from 2 rural towns in the Midwest. The questionnaire assessed the perceived social and physical environment, including neighborhood characteristics, as well as barriers to being active. The Kaiser Physical Activity Survey captured domain-specific activity levels. The response rate was 25%. Multiple regression analyses were conducted to examine the associations between social and physical environment factors and domain-specific physical activity. Having a favorable attitude toward using government funds for exercise and activity-friendly neighborhood characteristic were positively associated with active living. Friends encouraging exercise was positively associated with participation in sport. Barriers were inversely associated with active living and sport. Total physical activity was positively associated with workplace incentives for exercise, favorable policy attitudes toward supporting physical education in schools and supporting the use of government funds for biking trails, and it was inversely associated with barriers. There were no factors associated with physical activity in the domains of work or home care. Correlates of physical activity are unique to the domain in which this behavior occurs. Programs to increase physical activity in rural adults should target policy attitudes, neighborhood characteristics, and social support from friends while also working to decrease personal barriers to exercise. © 2014 National Rural Health Association.

ASH structure alignment package: Sensitivity and selectivity in domain classification

Directory of Open Access Journals (Sweden)

Toh Hiroyuki

2007-04-01

Full Text Available Abstract Background Structure alignment methods offer the possibility of measuring distant evolutionary relationships between proteins that are not visible by sequence-based analysis. However, the question of how structural differences and similarities ought to be quantified in this regard remains open. In this study we construct a training set of sequence-unique CATH and SCOP domains, from which we develop a scoring function that can reliably identify domains with the same CATH topology and SCOP fold classification. The score is implemented in the ASH structure alignment package, for which the source code and a web service are freely available from the PDBj website http://www.pdbj.org/ASH/. Results The new ASH score shows increased selectivity and sensitivity compared with values reported for several popular programs using the same test set of 4,298,905 structure pairs, yielding an area of .96 under the receiver operating characteristic (ROC curve. In addition, weak sequence homologies between similar domains are revealed that could not be detected by BLAST sequence alignment. Also, a subset of domain pairs is identified that exhibit high similarity, even though their CATH and SCOP classification differs. Finally, we show that the ranking of alignment programs based solely on geometric measures depends on the choice of the quality measure. Conclusion ASH shows high selectivity and sensitivity with regard to domain classification, an important step in defining distantly related protein sequence families. Moreover, the CPU cost per alignment is competitive with the fastest programs, making ASH a practical option for large-scale structure classification studies.

Structure of the C-terminal domain of lettuce necrotic yellows virus phosphoprotein.

Science.gov (United States)

Martinez, Nicolas; Ribeiro, Euripedes A; Leyrat, Cédric; Tarbouriech, Nicolas; Ruigrok, Rob W H; Jamin, Marc

2013-09-01

Lettuce necrotic yellows virus (LNYV) is a prototype of the plant-adapted cytorhabdoviruses. Through a meta-prediction of disorder, we localized a folded C-terminal domain in the amino acid sequence of its phosphoprotein. This domain consists of an autonomous folding unit that is monomeric in solution. Its structure, solved by X-ray crystallography, reveals a lollipop-shaped structure comprising five helices. The structure is different from that of the corresponding domains of other Rhabdoviridae, Filoviridae, and Paramyxovirinae; only the overall topology of the polypeptide chain seems to be conserved, suggesting that this domain evolved under weak selective pressure and varied in size by the acquisition or loss of functional modules.

Temperature-induced transitions between domain structures of ultrathin magnetic films

International Nuclear Information System (INIS)

Polyakova, T.; Zablotskii, V.

2005-01-01

Full text: Understanding of the influence of temperature on behavior of domain patterns of ultrathin magnetic films is of high significance for the fundamental physics of nanomagnetism as well as for technological applications. A thickness-dependent Curie temperature of ultrathin films may cause many interesting phenomena in the thermal evolution of domain structures (DS): i) nontrivial changes of the anisotropy constants as a function of the film thickness; ii) so-called inverse melting of DSs (processes where a more symmetric domain phase is found at lower temperatures than at higher temperatures - the inverse phase sequence) [1]; iii) temperature-induced transitions between domain structures. The possibility of such transitions is determined by lowering of the potential barriers separating different magnetization states as the film temperature approaches the Curie point. In this case with an increase of temperature, due to a significant decrease of the anisotropy constant, the domain wall energy is low enough and allows the system to reach equilibrium by a change of the domain wall number in the sample. This manifests itself in a transition from a metastable DS to a more stable DS which corresponds to new values of the anisotropy constant and magnetizations saturation. Thus, the temperature-induced transitions are driven by temperature changes of the magnetic parameters of the film. The key parameters controlling the DS geometry and period are the characteristic length, l c =σ/4πM S 2 (the ratio between the domain wall and demagnetization energies), and the quality factor Q =K/2πM S 2 (K is the first anisotropy constant). We show that for films with a pronounced nonmonotonic temperature dependence of l c one can expect a counter thermodynamic behavior: the inverse phase sequence and cooling-induced disordering. On changing temperature the existing domain structure should accommodate itself under new magnitudes of l c and Q. There are the two possible

Transcript structure and domain display: a customizable transcript visualization tool.

Science.gov (United States)

Watanabe, Kenneth A; Ma, Kaiwang; Homayouni, Arielle; Rushton, Paul J; Shen, Qingxi J

2016-07-01

Transcript Structure and Domain Display (TSDD) is a publicly available, web-based program that provides publication quality images of transcript structures and domains. TSDD is capable of producing transcript structures from GFF/GFF3 and BED files. Alternatively, the GFF files of several model organisms have been pre-loaded so that users only needs to enter the locus IDs of the transcripts to be displayed. Visualization of transcripts provides many benefits to researchers, ranging from evolutionary analysis of DNA-binding domains to predictive function modeling. TSDD is freely available for non-commercial users at http://shenlab.sols.unlv.edu/shenlab/software/TSD/transcript_display.html : jeffery.shen@unlv.nevada.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Multilevel domain decomposition for electronic structure calculations

International Nuclear Information System (INIS)

Barrault, M.; Cances, E.; Hager, W.W.; Le Bris, C.

2007-01-01

We introduce a new multilevel domain decomposition method (MDD) for electronic structure calculations within semi-empirical and density functional theory (DFT) frameworks. This method iterates between local fine solvers and global coarse solvers, in the spirit of domain decomposition methods. Using this approach, calculations have been successfully performed on several linear polymer chains containing up to 40,000 atoms and 200,000 atomic orbitals. Both the computational cost and the memory requirement scale linearly with the number of atoms. Additional speed-up can easily be obtained by parallelization. We show that this domain decomposition method outperforms the density matrix minimization (DMM) method for poor initial guesses. Our method provides an efficient preconditioner for DMM and other linear scaling methods, variational in nature, such as the orbital minimization (OM) procedure

Crystal Structure of the FERM Domain of Focal Adhesion Kinase

International Nuclear Information System (INIS)

Ceccarelli, D.; Song, H.; Poy, F.; Schaller, M.; Eck, M.

2006-01-01

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails of integrins, FAK promotes signaling events that modulate cellular growth, survival, and migration. The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain. FERM domains are found in a variety of signaling and cytoskeletal proteins and are thought to mediate intermolecular interactions with partner proteins and phospholipids at the plasma membrane and intramolecular regulatory interactions. Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains. The tertiary folds of the three subdomains (F1, F2, and F3) are similar to those of known FERM structures despite low sequence conservation. Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK. A putative protein interaction site on the F3 lobe is masked by the proximal region of the linker. Additionally, in one structure the adjacent Src SH3 and SH2 binding sites in the linker associate with the surfaces of the F3 and F1 lobes, respectively. These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment

C-terminal domains of bacterial proteases: structure, function and the biotechnological applications.

Science.gov (United States)

Huang, J; Wu, C; Liu, D; Yang, X; Wu, R; Zhang, J; Ma, C; He, H

2017-01-01

C-terminal domains widely exist in the C-terminal region of multidomain proteases. As a β-sandwich domain in multidomain protease, the C-terminal domain plays an important role in proteolysis including regulation of the secretory process, anchoring and swelling the substrate molecule, presenting as an inhibitor for the preprotease and adapting the protein structural flexibility and stability. In this review, the diversity, structural characteristics and biological function of C-terminal protease domains are described. Furthermore, the application prospects of C-terminal domains, including polycystic kidney disease, prepeptidase C-terminal and collagen-binding domain, in the area of medicine and biological artificial materials are also discussed. © 2016 The Society for Applied Microbiology.

Structures of BIR domains from human NAIP and cIAP2

International Nuclear Information System (INIS)

Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

2009-01-01

The crystal structures of the human NAIP BIR2 and cIAP2 BIR3 domains have been determined. Both BIR domains harbors an amino-terminal tetrapeptide in its peptide-binding groove. The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1′–P4′ side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3′ position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2′ and P4′ pockets make similar interactions to those seen in other BIR domain–peptide complexes. The structures also reveal how a serine in the P1′ position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins

Atomic resolution structure of the E. coli YajR transporter YAM domain

Energy Technology Data Exchange (ETDEWEB)

Jiang, Daohua [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Zhao, Yan [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China); Fan, Junping; Liu, Xuehui; Wu, Yan; Feng, Wei [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); Zhang, Xuejun C., E-mail: zhangc@ibp.ac.cn [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China)

2014-07-25

Highlights: • We report the crystal structure of the YAM domain of YajR transporter at 1.07 Å. • The YAM dimerization is related to the halogen-dependent high thermal stability. • A belt of poly-pentagonal water molecules was observed in the dimer interface. - Abstract: YajR is an Escherichia coli transporter that belongs to the major facilitator superfamily. Unlike most MFS transporters, YajR contains a carboxyl terminal, cytosolic domain of 67 amino acid residues termed YAM domain. Although it is speculated that the function of this small soluble domain is to regulate the conformational change of the 12-helix transmembrane domain, its precise regulatory role remains unclear. Here, we report the crystal structure of the YAM domain at 1.07-Å resolution, along with its structure determined using nuclear magnetic resonance. Detailed analysis of the high resolution structure revealed a symmetrical dimer in which a belt of well-ordered poly-pentagonal water molecules is embedded. A mutagenesis experiment and a thermal stability assay were used to analyze the putative role of this dimerization in response to changes in halogen concentration.

Structure of the C-Terminal Domain of Lettuce Necrotic Yellows Virus Phosphoprotein

Science.gov (United States)

Martinez, Nicolas; Ribeiro, Euripedes A.; Leyrat, Cédric; Tarbouriech, Nicolas; Ruigrok, Rob W. H.

2013-01-01

Lettuce necrotic yellows virus (LNYV) is a prototype of the plant-adapted cytorhabdoviruses. Through a meta-prediction of disorder, we localized a folded C-terminal domain in the amino acid sequence of its phosphoprotein. This domain consists of an autonomous folding unit that is monomeric in solution. Its structure, solved by X-ray crystallography, reveals a lollipop-shaped structure comprising five helices. The structure is different from that of the corresponding domains of other Rhabdoviridae, Filoviridae, and Paramyxovirinae; only the overall topology of the polypeptide chain seems to be conserved, suggesting that this domain evolved under weak selective pressure and varied in size by the acquisition or loss of functional modules. PMID:23785215

Structure discrimination for the C-terminal domain of Escherichia coli trigger factor in solution

International Nuclear Information System (INIS)

Yao Yong; Bhabha, Gira; Kroon, Gerard; Landes, Mindy; Dyson, H. Jane

2008-01-01

NMR measurements can give important information on solution structure, without the necessity for a full-scale solution structure determination. The C-terminal protein binding domain of the ribosome-associated chaperone protein trigger factor is composed of non-contiguous parts of the polypeptide chain, with an interpolated prolyl isomerase domain. A construct of the C-terminal domain of Escherichia coli trigger factor containing residues 113-149 and 247-432, joined by a Gly-Ser-Gly-Ser linker, is well folded and gives excellent NMR spectra in solution. We have used NMR measurements on this construct, and on a longer construct that includes the prolyl isomerase domain, to distinguish between two possible structures for the C-terminal domain of trigger factor, and to assess the behavior of the trigger factor C-terminal domain in solution. Two X-ray crystal structures, of intact trigger factor from E. coli (Ferbitz et al., Nature 431:590-596, 2004), and of a truncated trigger factor from Vibrio cholerae (Ludlam et al., Proc Natl Acad Sci USA 101:13436-13441, 2004) showed significant differences in the structure of the C-terminal domain, such that the two structures could not be superimposed. We show using NMR chemical shifts and long range nuclear Overhauser effects that the secondary and tertiary structure of the E. coli C-terminal domain in solution is consistent with the crystal structure of the E. coli trigger factor and not with the V. cholerae protein. Given the similarity of the amino acid sequences of the E. coli and V. cholerae proteins, it appears likely that the structure of the V. cholerae protein has been distorted as a result of truncation of a 44-amino acid segment at the C-terminus. Analysis of residual dipolar coupling measurements shows that the overall topology of the solution structure is completely inconsistent with both structures. Dynamics analysis of the C-terminal domain using T 1 , T 2 and heteronuclear NOE parameters show that the protein is

Is there a domain-general cognitive structuring system? Evidence from structural priming across music, math, action descriptions, and language.

Science.gov (United States)

Van de Cavey, Joris; Hartsuiker, Robert J

2016-01-01

Cognitive processing in many domains (e.g., sentence comprehension, music listening, and math solving) requires sequential information to be organized into an integrational structure. There appears to be some overlap in integrational processing across domains, as shown by cross-domain interference effects when for example linguistic and musical stimuli are jointly presented (Koelsch, Gunter, Wittfoth, & Sammler, 2005; Slevc, Rosenberg, & Patel, 2009). These findings support theories of overlapping resources for integrational processing across domains (cfr. SSIRH Patel, 2003; SWM, Kljajevic, 2010). However, there are some limitations to the studies mentioned above, such as the frequent use of unnaturalistic integrational difficulties. In recent years, the idea has risen that evidence for domain-generality in structural processing might also be yielded though priming paradigms (cfr. Scheepers, 2003). The rationale behind this is that integrational processing across domains regularly requires the processing of dependencies across short or long distances in the sequence, involving respectively less or more syntactic working memory resources (cfr. SWM, Kljajevic, 2010), and such processing decisions might persist over time. However, whereas recent studies have shown suggestive priming of integrational structure between language and arithmetics (though often dependent on arithmetic performance, cfr. Scheepers et al., 2011; Scheepers & Sturt, 2014), it remains to be investigated to what extent we can also find evidence for priming in other domains, such as music and action (cfr. SWM, Kljajevic, 2010). Experiment 1a showed structural priming from the processing of musical sequences onto the position in the sentence structure (early or late) to which a relative clause was attached in subsequent sentence completion. Importantly, Experiment 1b showed that a similar structural manipulation based on non-hierarchically ordered color sequences did not yield any priming effect

Structure of the USP15 N-terminal domains: a β-hairpin mediates close association between the DUSP and UBL domains.

Science.gov (United States)

Harper, Stephen; Besong, Tabot M D; Emsley, Jonas; Scott, David J; Dreveny, Ingrid

2011-09-20

Ubiquitin specific protease 15 (USP15) functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates. It influences the stability of adenomatous polyposis coli, IκBα, caspase-3, and the human papillomavirus type 16 E6. USP15 forms a subfamily with USP4 and USP11 related through a shared presence of N-terminal "domain present in ubiquitin specific proteases" (DUSP) and "ubiquitin-like" (UBL) domains (DU subfamily). Here we report the 1.5 Å resolution crystal structure of the human USP15 N-terminal domains revealing a 80 Å elongated arrangement with the DU domains aligned in tandem. This architecture is generated through formation of a defined interface that is dominated by an intervening β-hairpin structure (DU finger) that engages in an intricate hydrogen-bonding network between the domains. The UBL domain is closely related to ubiquitin among β-grasp folds but is characterized by the presence of longer loop regions and different surface characteristics, indicating that this domain is unlikely to act as ubiquitin mimic. Comparison with the related murine USP4 DUSP-UBL crystal structure reveals that the main DU interdomain contacts are conserved. Analytical ultracentrifugation, small-angle X-ray scattering, and gel filtration experiments revealed that USP15 DU is monomeric in solution. Our data provide a framework to advance study of the structure and function of the DU subfamily. © 2011 American Chemical Society

Structures of BIR domains from human NAIP and cIAP2.

Science.gov (United States)

Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

2009-11-01

The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.

Study of domain structure in segmented polyether polyurethaneureas by PAT

International Nuclear Information System (INIS)

Yin Chuanyuan; Xu Weizheng; Gu Qingchao

1990-01-01

The domain structure of segmented polyether polyurethaneureas is investigated by means of positron annihilation technique, small angle X-ray scattering and differential scanning calorimetry. The experimental results show that the decrease of domain volume and free volume results from the increase of hard segment contents, and that the increase of domain volume and free volume results from the increase of molecular weight of soft segments

Structure of Concatenated HAMP Domains Provides a Mechanism for Signal Transduction

Energy Technology Data Exchange (ETDEWEB)

Airola, Michael V.; Watts, Kylie J.; Bilwes, Alexandrine M.; Crane, Brian R. (Cornell); (Lorma Linda U)

2010-08-23

HAMP domains are widespread prokaryotic signaling modules found as single domains or poly-HAMP chains in both transmembrane and soluble proteins. The crystal structure of a three-unit poly-HAMP chain from the Pseudomonas aeruginosa soluble receptor Aer2 defines a universal parallel four-helix bundle architecture for diverse HAMP domains. Two contiguous domains integrate to form a concatenated di-HAMP structure. The three HAMP domains display two distinct conformations that differ by changes in helical register, crossing angle, and rotation. These conformations are stabilized by different subsets of conserved residues. Known signals delivered to HAMP would be expected to switch the relative stability of the two conformations and the position of a coiled-coil phase stutter at the junction with downstream helices. We propose that the two conformations represent opposing HAMP signaling states and suggest a signaling mechanism whereby HAMP domains interconvert between the two states, which alternate down a poly-HAMP chain.

Structure of the caspase-recruitment domain from a zebrafish guanylate-binding protein

International Nuclear Information System (INIS)

Jin, Tengchuan; Huang, Mo; Smith, Patrick; Jiang, Jiansheng; Xiao, T. Sam

2013-01-01

The crystal structure of the first zebrafish caspase-recruitment domain at 1.47 Å resolution illustrates a six-helix bundle fold similar to that of the human NLRP1 CARD. The caspase-recruitment domain (CARD) mediates homotypic protein–protein interactions that assemble large oligomeric signaling complexes such as the inflammasomes during innate immune responses. Structural studies of the mammalian CARDs demonstrate that their six-helix bundle folds belong to the death-domain superfamily, whereas such studies have not been reported for other organisms. Here, the zebrafish interferon-induced guanylate-binding protein 1 (zIGBP1) was identified that contains an N-terminal GTPase domain and a helical domain typical of the mammalian guanylate-binding proteins, followed by a FIIND domain and a C-terminal CARD similar to the mammalian inflammasome proteins NLRP1 and CARD8. The structure of the zIGBP1 CARD as a fusion with maltose-binding protein was determined at 1.47 Å resolution. This revealed a six-helix bundle fold similar to the NLRP1 CARD structure with the bent α1 helix typical of all known CARD structures. The zIGBP1 CARD surface contains a positively charged patch near its α1 and α4 helices and a negatively charged patch near its α2, α3 and α5 helices, which may mediate its interaction with partner domains. Further studies using binding assays and other analyses will be required in order to address the physiological function(s) of this zebrafish protein

Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

Energy Technology Data Exchange (ETDEWEB)

Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [Pathology and Microbiology Department, 986495 Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

2011-05-01

The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite N. americanus refined to a resolution limit of 2.2 Å is presented. Major proteins secreted by the infective larval stage hookworms upon host entry include Ancylostoma secreted proteins (ASPs), which are characterized by one or two CAP (cysteine-rich secretory protein/antigen 5/pathogenesis related-1) domains. The CAP domain has been reported in diverse phylogenetically unrelated proteins, but has no confirmed function. The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structure was solved by molecular replacement (MR) using Na-ASP-2, a one-CAP-domain ASP, as the search model. The correct MR solution could only be obtained by truncating the polyalanine model of Na-ASP-2 and removing several loops. The structure reveals two CAP domains linked by an extended loop. Overall, the carboxyl-terminal CAP domain is more similar to Na-ASP-2 than to the amino-terminal CAP domain. A large central cavity extends from the amino-terminal CAP domain to the carboxyl-terminal CAP domain, encompassing the putative CAP-binding cavity. The putative CAP-binding cavity is a characteristic cavity in the carboxyl-terminal CAP domain that contains a His and Glu pair. These residues are conserved in all single-CAP-domain proteins, but are absent in the amino-terminal CAP domain. The conserved His residues are oriented such that they appear to be capable of directly coordinating a zinc ion as observed for CAP proteins from reptile venoms. This first structure of a two-CAP-domain ASP can serve as a template for homology modeling of other two-CAP-domain proteins.

Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

International Nuclear Information System (INIS)

Asojo, Oluwatoyin A.

2011-01-01

The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite N. americanus refined to a resolution limit of 2.2 Å is presented. Major proteins secreted by the infective larval stage hookworms upon host entry include Ancylostoma secreted proteins (ASPs), which are characterized by one or two CAP (cysteine-rich secretory protein/antigen 5/pathogenesis related-1) domains. The CAP domain has been reported in diverse phylogenetically unrelated proteins, but has no confirmed function. The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structure was solved by molecular replacement (MR) using Na-ASP-2, a one-CAP-domain ASP, as the search model. The correct MR solution could only be obtained by truncating the polyalanine model of Na-ASP-2 and removing several loops. The structure reveals two CAP domains linked by an extended loop. Overall, the carboxyl-terminal CAP domain is more similar to Na-ASP-2 than to the amino-terminal CAP domain. A large central cavity extends from the amino-terminal CAP domain to the carboxyl-terminal CAP domain, encompassing the putative CAP-binding cavity. The putative CAP-binding cavity is a characteristic cavity in the carboxyl-terminal CAP domain that contains a His and Glu pair. These residues are conserved in all single-CAP-domain proteins, but are absent in the amino-terminal CAP domain. The conserved His residues are oriented such that they appear to be capable of directly coordinating a zinc ion as observed for CAP proteins from reptile venoms. This first structure of a two-CAP-domain ASP can serve as a template for homology modeling of other two-CAP-domain proteins

Structure of the Ebola VP35 interferon inhibitory domain.

Science.gov (United States)

Leung, Daisy W; Ginder, Nathaniel D; Fulton, D Bruce; Nix, Jay; Basler, Christopher F; Honzatko, Richard B; Amarasinghe, Gaya K

2009-01-13

Ebola viruses (EBOVs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. The Ebola VP35 protein is multifunctional, acting as a component of the viral RNA polymerase complex, a viral assembly factor, and an inhibitor of host interferon (IFN) production. Mutation of select basic residues within the C-terminal half of VP35 abrogates its dsRNA-binding activity, impairs VP35-mediated IFN antagonism, and attenuates EBOV growth in vitro and in vivo. Because VP35 contributes to viral escape from host innate immunity and is required for EBOV virulence, understanding the structural basis for VP35 dsRNA binding, which correlates with suppression of IFN activity, is of high importance. Here, we report the structure of the C-terminal VP35 IFN inhibitory domain (IID) solved to a resolution of 1.4 A and show that VP35 IID forms a unique fold. In the structure, we identify 2 basic residue clusters, one of which is important for dsRNA binding. The dsRNA binding cluster is centered on Arg-312, a highly conserved residue required for IFN inhibition. Mutation of residues within this cluster significantly changes the surface electrostatic potential and diminishes dsRNA binding activity. The high-resolution structure and the identification of the conserved dsRNA binding residue cluster provide opportunities for antiviral therapeutic design. Our results suggest a structure-based model for dsRNA-mediated innate immune antagonism by Ebola VP35 and other similarly constructed viral antagonists.

Structure determination of human Lck unique and SH3 domains by nuclear magnetic resonance spectroscopy

Directory of Open Access Journals (Sweden)

Willbold Dieter

2003-05-01

Full Text Available Abstract Background Protein tyrosine kinases are involved in signal transduction pathways that regulate cell growth, differentiation, activation and transformation. Human lymphocyte specific kinase (Lck is a 56 kDa protein involved in T-cell- and IL2-receptor signaling. Three-dimensional structures are known for SH3, SH2 and kinase domains of Lck as well as for other tyrosine kinases. No structure is known for the unique domain of any Src-type tyrosine kinase. Results Lck(1–120 comprising unique and SH3 domains was structurally investigated by nuclear magnetic resonance spectroscopy. We found the unique domain, in contrast to the SH3 part, to have basically no defined structural elements. The solution structure of the SH3 part could be determined with very high precision. It does not show significant differences to Lck SH3 in the absence of the unique domain. Minor differences were observed to the X-ray structure of Lck SH3. Conclusion The unique domain of Lck does not contain any defined structure elements in the absence of ligands and membranes. Presence of the unique domain is not relevant to the three-dimensional structure of the Lck SH3 domain.

Correlation Structures of Correlated Binomial Models and Implied Default Distribution

OpenAIRE

S. Mori; K. Kitsukawa; M. Hisakado

2006-01-01

We show how to analyze and interpret the correlation structures, the conditional expectation values and correlation coefficients of exchangeable Bernoulli random variables. We study implied default distributions for the iTraxx-CJ tranches and some popular probabilistic models, including the Gaussian copula model, Beta binomial distribution model and long-range Ising model. We interpret the differences in their profiles in terms of the correlation structures. The implied default distribution h...

Ferroelectric domain continuity over grain boundaries

DEFF Research Database (Denmark)

Mantri, Sukriti; Oddershede, Jette; Damjanovic, Dragan

2017-01-01

Formation and mobility of domain walls in ferroelectric materials is responsible for many of their electrical and mechanical properties. Domain wall continuity across grain boundaries has been observed since the 1950's and is speculated to affect the grain boundary-domain interactions, thereby...... impacting macroscopic ferroelectric properties in polycrystalline systems. However detailed studies of such correlated domain structures across grain boundaries are limited. In this work, we have developed the mathematical requirements for domain wall plane matching at grain boundaries of any given...... orientation. We have also incorporated the effect of grain boundary ferroelectric polarization charge created when any two domains meet at the grain boundary plane. The probability of domain wall continuity for three specific grain misorientations is studied. Use of this knowledge to optimize processing...

Analysis and modelling of engineering structures in frequency domain

International Nuclear Information System (INIS)

Ishtev, K.; Bonev, Z.; Petrov, P.; Philipov, P.

1987-01-01

This paper deals with some possible applications for modelling and analysis of engineering structures, basing on technique, mentioned above. The governing system of equations is written by using frequency domain approach since elemination technique has computational significance in this field. Modelling is made basing on the well known relationship Y(jw) = W(jw) * X(jw). Here X(jw) is a complex Fourier spectra associated with the imput signals being defined as earthquake, wind, hydrodynamic, control or other type of action. W(jw) is a matrix complex transfer function which reveals the correlation between input X und output Y spectra. Y (ja) represents a complex Fourier spectra of output signals. Input and output signals are both associated with master degrees of freedom, thus matrix transfer function is composed of elements in such a manner that solve unknown parameters are implemented implicitly. It is available an integration algorithm of 'condensed' system of equations. (orig./GL)

Correlation between hierarchical structure of crystal networks and macroscopic performance of mesoscopic soft materials and engineering principles.

Science.gov (United States)

Lin, Naibo; Liu, Xiang Yang

2015-11-07

This review examines how the concepts and ideas of crystallization can be extended further and applied to the field of mesoscopic soft materials. It concerns the structural characteristics vs. the macroscopic performance, and the formation mechanism of crystal networks. Although this subject can be discussed in a broad sense across the area of mesoscopic soft materials, our main focus is on supramolecular materials, spider and silkworm silks, and biominerals. First, the occurrence of a hierarchical structure, i.e. crystal network and domain network structures, will facilitate the formation kinetics of mesoscopic phases and boost up the macroscopic performance of materials in some cases (i.e. spider silk fibres). Second, the structure and performance of materials can be correlated in some way by the four factors: topology, correlation length, symmetry/ordering, and strength of association of crystal networks. Moreover, four different kinetic paths of crystal network formation are identified, namely, one-step process of assembly, two-step process of assembly, mixed mode of assembly and foreign molecule mediated assembly. Based on the basic mechanisms of crystal nucleation and growth, the formation of crystal networks, such as crystallographic mismatch (or noncrystallographic) branching (tip branching and fibre side branching) and fibre/polymeric side merging, are reviewed. This facilitates the rational design and construction of crystal networks in supramolecular materials. In this context, the (re-)construction of a hierarchical crystal network structure can be implemented by thermal, precipitate, chemical, and sonication stimuli. As another important class of soft materials, the unusual mechanical performance of spider and silkworm silk fibres are reviewed in comparison with the regenerated silk protein derivatives. It follows that the considerably larger breaking stress and unusual breaking strain of spider silk fibres vs. silkworm silk fibres can be interpreted

A systematic classification of Plasmodium falciparum P-loop NTPases: structural and functional correlation

Directory of Open Access Journals (Sweden)

Chauhan Virander S

2009-04-01

Full Text Available Abstract Background The P-loop NTPases constitute one of the largest groups of globular protein domains that play highly diverse functional roles in most of the organisms. Even with the availability of nearly 300 different Hidden Markov Models representing the P-loop NTPase superfamily, not many P-loop NTPases are known in Plasmodium falciparum. A number of characteristic attributes of the genome have resulted into the lack of knowledge about this functionally diverse, but important class of proteins. Method In the study, protein sequences with characteristic motifs of NTPase domain (Walker A and Walker B are computationally extracted from the P. falciparum database. A detailed secondary structure analysis, functional classification, phylogenetic and orthology studies of the NTPase domain of repertoire of 97 P. falciparum P-loop NTPases is carried out. Results Based upon distinct sequence features and secondary structure profile of the P-loop domain of obtained sequences, a cladistic classification is also conceded: nucleotide kinases and GTPases, ABC and SMC family, SF1/2 helicases, AAA+ and AAA protein families. Attempts are made to identify any ortholog(s for each of these proteins in other Plasmodium sp. as well as its vertebrate host, Homo sapiens. A number of P. falciparum P-loop NTPases that have no homologue in the host, as well as those annotated as hypothetical proteins and lack any characteristic functional domain are identified. Conclusion The study suggests a strong correlation between sequence and secondary structure profile of P-loop domains and functional roles of these proteins and thus provides an opportunity to speculate the role of many hypothetical proteins. The study provides a methodical framework for the characterization of biologically diverse NTPases in the P. falciparum genome. The efforts made in the analysis are first of its kind; and the results augment to explore the functional role of many of these proteins from

Structure of the first PDZ domain of human PSD-93

DEFF Research Database (Denmark)

Fiorentini, Monica; Nielsen, Ann Kallehauge; Kristensen, Ole

2009-01-01

The crystal structure of the PDZ1 domain of human PSD-93 has been determined to 2.0 A resolution. The PDZ1 domain forms a crystallographic trimer that is also predicted to be stable in solution. The main contributions to the stabilization of the trimer seem to arise from interactions involving...... the PDZ1-PDZ2 linker region at the extreme C-terminus of PDZ1, implying that the oligomerization that is observed is not of biological significance in full-length PSD-93. Comparison of the structures of the binding cleft of PSD-93 PDZ1 with the previously reported structures of PSD-93 PDZ2 and PDZ3...

Structural-Functional Analysis Reveals a Specific Domain Organization in Family GH20 Hexosaminidases.

Science.gov (United States)

Val-Cid, Cristina; Biarnés, Xevi; Faijes, Magda; Planas, Antoni

2015-01-01

Hexosaminidases are involved in important biological processes catalyzing the hydrolysis of N-acetyl-hexosaminyl residues in glycosaminoglycans and glycoconjugates. The GH20 enzymes present diverse domain organizations for which we propose two minimal model architectures: Model A containing at least a non-catalytic GH20b domain and the catalytic one (GH20) always accompanied with an extra α-helix (GH20b-GH20-α), and Model B with only the catalytic GH20 domain. The large Bifidobacterium bifidum lacto-N-biosidase was used as a model protein to evaluate the minimal functional unit due to its interest and structural complexity. By expressing different truncated forms of this enzyme, we show that Model A architectures cannot be reduced to Model B. In particular, there are two structural requirements general to GH20 enzymes with Model A architecture. First, the non-catalytic domain GH20b at the N-terminus of the catalytic GH20 domain is required for expression and seems to stabilize it. Second, the substrate-binding cavity at the GH20 domain always involves a remote element provided by a long loop from the catalytic domain itself or, when this loop is short, by an element from another domain of the multidomain structure or from the dimeric partner. Particularly, the lacto-N-biosidase requires GH20b and the lectin-like domain at the N- and C-termini of the catalytic GH20 domain to be fully soluble and functional. The lectin domain provides this remote element to the active site. We demonstrate restoration of activity of the inactive GH20b-GH20-α construct (model A architecture) by a complementation assay with the lectin-like domain. The engineering of minimal functional units of multidomain GH20 enzymes must consider these structural requirements.

Functional Properties at Domain Walls in BiFeO3: Electrical, Magnetic, and Structural investigations

Science.gov (United States)

He, Qing; Yang, C.-H.; Yu, P.; Gajek, M.; Seidel, J.; Ramesh, R.; Wang, F.; Chu, Y.-H.; Martin, L. W.; Spaldin, N.; Rother, A.

2009-03-01

BiFeO3 (BFO) is a widely studied robust ferroelectric, antiferromagnetic multiferroic. Conducting-atomic force microscopy studies reveal the presence of enhanced conductivity at certain types of domain walls in BFO. We have completed detailed TEM studies of the physical structure at these domain walls as well as in-depth DFT calculations of the evolution of electronic structure at these domain walls. These studies reveal two major contributions to the observed conduction: the formation of an electrostatic potential at the domain walls as well as a structurally-driven change in the electronic structure (i.e., a lower band gap locally) at the domain walls. We will discuss the use of optical characterization techniques as a way of probing this change in electronic structure at domain walls as well as detailed IV characterization both in atmospheric and UHV environments. Finally, the evolution of magnetism at these domain walls has been studied through the use of photoemission measurements. Initial findings point to a significant change in the magnetic order at these domain walls in BFO.

Time domain structures in a colliding magnetic flux rope experiment

Science.gov (United States)

Tang, Shawn Wenjie; Gekelman, Walter; Dehaas, Timothy; Vincena, Steve; Pribyl, Patrick

2017-10-01

Electron phase-space holes, regions of positive potential on the scale of the Debye length, have been observed in auroras as well as in laboratory experiments. These potential structures, also known as Time Domain Structures (TDS), are packets of intense electric field spikes that have significant components parallel to the local magnetic field. In an ongoing investigation at UCLA, TDS were observed on the surface of two magnetized flux ropes produced within the Large Plasma Device (LAPD). A barium oxide (BaO) cathode was used to produce an 18 m long magnetized plasma column and a lanthanum hexaboride (LaB6) source was used to create 11 m long kink unstable flux ropes. Using two probes capable of measuring the local electric and magnetic fields, correlation analysis was performed on tens of thousands of these structures and their propagation velocities, probability distribution function and spatial distribution were determined. The TDS became abundant as the flux ropes collided and appear to emanate from the reconnection region in between them. In addition, a preliminary analysis of the permutation entropy and statistical complexity of the data suggests that the TDS signals may be chaotic in nature. Work done at the Basic Plasma Science Facility (BaPSF) at UCLA which is supported by DOE and NSF.

Magnetic domain structure of MnAs thin films as a function of temperature

International Nuclear Information System (INIS)

Mizuguchi, Masaki; Manago, Takashi; Akinaga, Hiroyuki; Kuramochi, Hiromi; Okabayashi, Jun

2003-01-01

We have investigate magnetic domain structures of MnAs thin films grown on GaAs substrates by a magnetic force microscope. We observed, by an atomic force microscope, rectangular defects along GaAs [110] direction which disperse randomly on the surface of MnAs/GaAs(001). The Curie temperature of MnAs is 45degC, and it is successfully confirmed directly by the variable temperature magnetic force microscope observation. We also investigated magnetic domain structures of MnAs/GaAs(111)B, and no apparent relation was observed between the topographic structure and the magnetic domain structure. (author)

Effect of ferroelastic domain pattern changes on the EPR spectra in TDM

Science.gov (United States)

Zapart, W.; Zapart, M. B.

2011-09-01

This article presents polarized light microscopy studies of the ferroelastic domain structure and the analysis of electron paramagnetic resonance spectra of Cr3+ admixture ions in trigonal double molybdates. The correlation has been found between abnormal EPR lineshape and domain structure in ferroelastic phases of these crystals.

Nuclear correlations and structure functions

International Nuclear Information System (INIS)

Hu Guoju; Irvine, J.M.

1989-01-01

It is argued that the search for a mass number dependence of the nuclear structure function per nucleon is profitably directed to the region of Bjorken scaling variable x > 1. We show that in the convolution model of the nuclear structure function the nuclear momentum distribution and energy spectrum generated by cluster expansion techniques, here realised in the correlated basis function method, invoking tensor correlations and short-range density-dependent repulsions adequately describes the structure function for 12 C in the region x > 1. The results of structure functions for a number of light-, medium- and heavy-mass nuclei are presented. (author)

Structure of a WW domain-containing fragment of dystrophin complexed with {beta}-dystroglycan.

Energy Technology Data Exchange (ETDEWEB)

Huang, X.; Poy, F.; Zhang, R.; Joachimiak, A.; Sudol, M.; Eck, M. J.; Biosciences Division; Dana Farber Cancer Inst.; Harvard Medical School; Mount Sinai School of Medicine

2000-08-01

Dystrophin and {beta}-dystroglycan are components of the dystrophin--glycoprotein complex (DGC), a multimolecular assembly that spans the cell membrane and links the actin cytoskeleton to the extracellular basal lamina. Defects in the dystrophin gene are the cause of Duchenne and Becker muscular dystrophies. The C-terminal region of dystrophin binds the cytoplasmic tail of {beta}-dystroglycan, in part through the interaction of its WW domain with a proline-rich motif in the tail of {beta}-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich binding site in {beta}-dystroglycan. The structure shows that the dystrophin WW domain is embedded in an adjacent helical region that contains two EF-hand-like domains. The {beta}-dystroglycan peptide binds a composite surface formed by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition employed by WW domains and SH3 domains.

Structure of the EMMPRIN N-terminal domain 1: Dimerization via [beta]-strand swapping

Energy Technology Data Exchange (ETDEWEB)

Luo, Jinquan; Teplyakov, Alexey; Obmolova, Galina; Malia, Thomas; Wu, Sheng-Jiun; Beil, Eric; Baker, Audrey; Swencki-Underwood, Bethany; Zhao, Yonghong; Sprenkle, Justin; Dixon, Ken; Sweet, Raymond; Gilliland, Gary L.; (Centocor)

2010-09-27

Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as Hab18G, CD147, Basigin, M6, and neurothelin, is a membrane glycoprotein expressed on the surface of various cell types and many cancer cells. EMMPRIN stimulates adjacent fibroblasts and tumor cells to produce matrix metalloproteinases and plays an important role in tumor invasion and metastasis, angiogenesis, spermatogensis and fertilization, cell-cell adhesion and communication, and other biological processes (reviewed in Ref. 1 and references therein). It was demonstrated that the EMMPRIN extracellular domain (ECD), which structurally belongs to the IgG superfamily, can form homo-oligomers in a cis dependent manner and the N-terminal domain 1 (residues 22-101) was necessary and sufficient to mediate this interaction. The crystal structure of the ECD of recombinant human EMMPRIN (Hab18G/CD147) expressed in E. coli was reported at 2.8 {angstrom} resolution (Yu et al. 2008). The construct consists of residues 22-205 of the mature protein and has both an N-terminal IgC2 domain (ND1, residues 22-101) and a C-terminal IgC2 domain (ND2, residues 107-205). The two domains are joined by a five amino acid residue linker that constitutes a flexible hinge between the two domains. The crystal form has four copies of the molecule in the asymmetric unit, each of which has a different inter-domain angle that varies from 121{sup o} to 144{sup o}. The two domains each have a conserved disulfide bridge and both are comprised of two {beta}-sheets formed by strands EBA and GFCC, and DEBA and AGFCC for ND1 and ND2, respectively. Based on the crystal packing in this structure, the authors proposed that lateral packing between the two IgG domains of EMMPRIN ECD represents a potential mechanism for cell adhesion. Here we report the 2.0-{angstrom} crystal structure of the N-terminal domain of EMMPRIN ECD (ND1) expressed in mammalian cells. The overall structure of the domain is very similar to that in the full length

A model for the magnetic domain structure of Gd at 77K

International Nuclear Information System (INIS)

Corner, W.D.; Saad, F.M.; Jones, D.W.; Jordan, R.G.

1978-01-01

Magnetic domain structures have been observed on planes perpendicular to the c and b axes of Gd crystals at 77K. Various types of domain boundary which might be found in an easy-cone ferromagnet are discussed. A model is presented which is consistent with observations. In this the easy-cone structure is maintained, but it is assumed that owing to the lower basal-plane anisotropy the magnetization component in the basal plane may change in direction within a single domain. (author)

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

Structural Studies of the SET Domain from RIZ1 Tumor Suppressor

Energy Technology Data Exchange (ETDEWEB)

Briknarova, Klara; Zhou, Xinliang; Satterthwait, Arnold C.; Hoyt, David W.; Ely, Kathryn R.; Huang, Shi

2008-02-15

Histone lysine methyltransferases (HKMTs) are involved in regulation of chromatin structure, and, as such, are important for longterm gene activation and repression that is associated with cell memory and establishment of cell-type specific transcriptional programs. Most HKMTs contain a SET domain, which is responsible for their catalytic activity. RIZ1 is a transcription regulator and tumor suppressor that catalyzes methylation of lysine 9 of histone H3 and contains a rather distinct SET domain. Similar SET domains, sometimes refererred to as PR (PRDI-BF1 and RIZ1 homology) domains, are also found in other proteins including Blimp-1/PRDI-BF1, MDS1-EVI1 and Meisetz. We determined the solution structure of the PR domain from RIZ1 and characterized its interaction with S-adenosyl homocysteine (SAH) and a peptide from histone H3. Despite low sequence identity with canonical SET domains, the PR domain displays a typical SET fold including a pseudo-knot at the C-terminus. The N-flanking sequence of RIZ1 PR domain adopts a novel conformation and interacts closely with the SET fold. The C-flanking sequence contains an α-helix that exhibits higher mobility than the SET fold and points away from the protein face that harbors active site in other SET domains. Residues that interact with the methylation cofactor in SET domains are not conserved in RIZ1 or other PR domains, and the SET fold of RIZ1 does not bind SAH. However, the PR domain of RIZ1 interacts specifically with a synthetic peptide comprising residues 1-20 of histone H3.

Structural Time Domain Identification Toolbox User's Guide

DEFF Research Database (Denmark)

Andersen, P.; Kirkegaard, Poul Henning; Brincker, Rune

This manual describes the Structural Time Domain Identification toolbox for use with MA TLAB. This version of the tool box has been developed using the PC-based MA TLAB version 4.2c, but is compatible with prior versions of MATLAB and UNIX-based versions. The routines of the toolbox are the so...

Models for randomly distributed nanoscopic domains on spherical vesicles

Science.gov (United States)

Anghel, Vinicius N. P.; Bolmatov, Dima; Katsaras, John

2018-06-01

The existence of lipid domains in the plasma membrane of biological systems has proven controversial, primarily due to their nanoscopic size—a length scale difficult to interrogate with most commonly used experimental techniques. Scattering techniques have recently proven capable of studying nanoscopic lipid domains populating spherical vesicles. However, the development of analytical methods able of predicting and analyzing domain pair correlations from such experiments has not kept pace. Here, we developed models for the random distribution of monodisperse, circular nanoscopic domains averaged on the surface of a spherical vesicle. Specifically, the models take into account (i) intradomain correlations corresponding to form factors and interdomain correlations corresponding to pair distribution functions, and (ii) the analytical computation of interdomain correlations for cases of two and three domains on a spherical vesicle. In the case of more than three domains, these correlations are treated either by Monte Carlo simulations or by spherical analogs of the Ornstein-Zernike and Percus-Yevick (PY) equations. Importantly, the spherical analog of the PY equation works best in the case of nanoscopic size domains, a length scale that is mostly inaccessible by experimental approaches such as, for example, fluorescent techniques and optical microscopies. The analytical form factors and structure factors of nanoscopic domains populating a spherical vesicle provide a new and important framework for the quantitative analysis of experimental data from commonly studied phase-separated vesicles used in a wide range of biophysical studies.

Eukaryotic ribonucleases P/MRP: the crystal structure of the P3 domain.

Science.gov (United States)

Perederina, Anna; Esakova, Olga; Quan, Chao; Khanova, Elena; Krasilnikov, Andrey S

2010-02-17

Ribonuclease (RNase) P is a site-specific endoribonuclease found in all kingdoms of life. Typical RNase P consists of a catalytic RNA component and a protein moiety. In the eukaryotes, the RNase P lineage has split into two, giving rise to a closely related enzyme, RNase MRP, which has similar components but has evolved to have different specificities. The eukaryotic RNases P/MRP have acquired an essential helix-loop-helix protein-binding RNA domain P3 that has an important function in eukaryotic enzymes and distinguishes them from bacterial and archaeal RNases P. Here, we present a crystal structure of the P3 RNA domain from Saccharomyces cerevisiae RNase MRP in a complex with RNase P/MRP proteins Pop6 and Pop7 solved to 2.7 A. The structure suggests similar structural organization of the P3 RNA domains in RNases P/MRP and possible functions of the P3 domains and proteins bound to them in the stabilization of the holoenzymes' structures as well as in interactions with substrates. It provides the first insight into the structural organization of the eukaryotic enzymes of the RNase P/MRP family.

Variability and conservation of structural domains in divide-and-conquer approaches

Energy Technology Data Exchange (ETDEWEB)

Wiegand, Thomas [ETH Zurich, Physical Chemistry (Switzerland); Gardiennet, Carole [CNRS, Université de Lorraine, CRM2, UMR 7036 (France); Cadalbert, Riccardo [ETH Zurich, Physical Chemistry (Switzerland); Lacabanne, Denis; Kunert, Britta; Terradot, Laurent, E-mail: laurent.terradot@ibcp.fr; Böckmann, Anja, E-mail: a.bockmann@ibcp.fr [Université de Lyon, Institut de Biologie et Chimie des Protéines, Bases Moléculaires et Structurales des Systèmes Infectieux, Labex Ecofect, UMR 5086 CNRS (France); Meier, Beat H., E-mail: beme@ethz.ch [ETH Zurich, Physical Chemistry (Switzerland)

2016-06-15

The use of protein building blocks for the structure determination of multidomain proteins and protein–protein complexes, also known as the “divide and conquer” approach, is an important strategy for obtaining protein structures. Atomic-resolution X-ray or NMR data of the individual domains are combined with lower-resolution electron microscopy maps or X-ray data of the full-length protein or the protein complex. Doing so, it is often assumed that the individual domain structures remain invariant in the context of the superstructure. In this work, we show the potentials and limitations of NMR to validate this approach at the example of the dodecameric DnaB helicase from Helicobacter pylori. We investigate how sequentially assigned spectra, as well as unassigned spectral fingerprints can be used to indicate the conservation of individual domains, and also to highlight conformational differences.

Magnetic domain structure and domain-wall energy in UFe8Ni2Si2 and UFe6Ni4Si2 intermetallic compounds

International Nuclear Information System (INIS)

Wyslocki, J.J.; Suski, W.; Wochowski, K.

1994-01-01

Magnetic domain structures in the UFe 8 Ni 2 Si 2 and UFe 6 Ni 4 Si 2 compounds were studied using the powder pattern method. The domain structure observed is typical for uniaxial materials. The domain-wall energy density γ was determined from the average surface domain width D s observed on surfaces perpendicular to the easy axis as equal to 16 erg/cm 2 for UFe 8 Ni 2 Si 2 and 10 erg/cm 2 for UFe 6 Ni 4 Si 2 . Moreover, the critical diameter for single domain particle D c was calculated for the studied compounds

The crystal structures of EAP domains from Staphylococcus aureus reveal an unexpected homology to bacterial superantigens.

Science.gov (United States)

Geisbrecht, Brian V; Hamaoka, Brent Y; Perman, Benjamin; Zemla, Adam; Leahy, Daniel J

2005-04-29

The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 A resolution, respectively. These structures reveal a core fold that is comprised of an alpha-helix lying diagonally across a five-stranded, mixed beta-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the beta-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

Structural interactions between lipids, water and S1-S4 voltage-sensing domains.

Science.gov (United States)

Krepkiy, Dmitriy; Gawrisch, Klaus; Swartz, Kenton J

2012-11-02

Membrane proteins serve crucial signaling and transport functions, yet relatively little is known about their structures in membrane environments or how lipids interact with these proteins. For voltage-activated ion channels, X-ray structures suggest that the mobile voltage-sensing S4 helix would be exposed to the membrane, and functional studies reveal that lipid modification can profoundly alter channel activity. Here, we use solid-state NMR to investigate structural interactions of lipids and water with S1-S4 voltage-sensing domains and to explore whether lipids influence the structure of the protein. Our results demonstrate that S1-S4 domains exhibit extensive interactions with lipids and that these domains are heavily hydrated when embedded in a membrane. We also find evidence for preferential interactions of anionic lipids with S1-S4 domains and that these interactions have lifetimes on the timescale of ≤ 10(-3)s. Arg residues within S1-S4 domains are well hydrated and are positioned in close proximity to lipids, exhibiting local interactions with both lipid headgroups and acyl chains. Comparative studies with a positively charged lipid lacking a phosphodiester group reveal that this lipid modification has only modest effects on the structure and hydration of S1-S4 domains. Taken together, our results demonstrate that Arg residues in S1-S4 voltage-sensing domains reside in close proximity to the hydrophobic interior of the membrane yet are well hydrated, a requirement for carrying charge and driving protein motions in response to changes in membrane voltage. Published by Elsevier Ltd.

Mutiple LDPC Decoding using Bitplane Correlation for Transform Domain Wyner-Ziv Video Coding

DEFF Research Database (Denmark)

Luong, Huynh Van; Huang, Xin; Forchhammer, Søren

2011-01-01

Distributed video coding (DVC) is an emerging video coding paradigm for systems which fully or partly exploit the source statistics at the decoder to reduce the computational burden at the encoder. This paper considers a Low Density Parity Check (LDPC) based Transform Domain Wyner-Ziv (TDWZ) video...... codec. To improve the LDPC coding performance in the context of TDWZ, this paper proposes a Wyner-Ziv video codec using bitplane correlation through multiple parallel LDPC decoding. The proposed scheme utilizes inter bitplane correlation to enhance the bitplane decoding performance. Experimental results...

Structure of the nucleotide-binding domain of a dipeptide ABC transporter reveals a novel iron-sulfur cluster-binding domain.

Science.gov (United States)

Li, Xiaolu; Zhuo, Wei; Yu, Jie; Ge, Jingpeng; Gu, Jinke; Feng, Yue; Yang, Maojun; Wang, Linfang; Wang, Na

2013-02-01

Dipeptide permease (Dpp), which belongs to an ABC transport system, imports peptides consisting of two or three L-amino acids from the matrix to the cytoplasm in microbes. Previous studies have indicated that haem competes with dipeptides to bind DppA in vitro and in vivo and that the Dpp system can also translocate haem. Here, the crystal structure of DppD, the nucleotide-binding domain (NBD) of the ABC-type dipeptide/oligopeptide/nickel-transport system from Thermoanaerobacter tengcongensis, bound with ATP, Mg(2+) and a [4Fe-4S] iron-sulfur cluster is reported. The N-terminal domain of DppD shares a similar structural fold with the NBDs of other ABC transporters. Interestingly, the C-terminal domain of DppD contains a [4Fe-4S] cluster. The UV-visible absorbance spectrum of DppD was consistent with the presence of a [4Fe-4S] cluster. A search with DALI revealed that the [4Fe-4S] cluster-binding domain is a novel structural fold. Structural analysis and comparisons with other ABC transporters revealed that this iron-sulfur cluster may act as a mediator in substrate (dipeptide or haem) binding by electron transfer and may regulate the transport process in Dpp ABC transport systems. The crystal structure provides a basis for understanding the properties of ABC transporters and will be helpful in investigating the functions of NBDs in the regulation of ABC transporter activity.

Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.

Science.gov (United States)

Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G

2015-06-01

The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.

Structure of the Nucleoprotein Binding Domain of Mokola Virus Phosphoprotein▿

Science.gov (United States)

Assenberg, René; Delmas, Olivier; Ren, Jingshan; Vidalain, Pierre-Olivier; Verma, Anil; Larrous, Florence; Graham, Stephen C.; Tangy, Frédéric; Grimes, Jonathan M.; Bourhy, Hervé

2010-01-01

Mokola virus (MOKV) is a nonsegmented, negative-sense RNA virus that belongs to the Lyssavirus genus and Rhabdoviridae family. MOKV phosphoprotein P is an essential component of the replication and transcription complex and acts as a cofactor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. Here we present a structure for this domain of MOKV P, obtained by expression of full-length P in Escherichia coli, which was subsequently truncated during crystallization. The structure has a high degree of homology with P of rabies virus, another member of Lyssavirus genus, and to a lesser degree with P of vesicular stomatitis virus (VSV), a member of the related Vesiculovirus genus. In addition, analysis of the crystal packing of this domain reveals a potential binding site for the nucleoprotein N. Using both site-directed mutagenesis and yeast two-hybrid experiments to measure P-N interaction, we have determined the relative roles of key amino acids involved in this interaction to map the region of P that binds N. This analysis also reveals a structural relationship between the N-RNA binding domain of the P proteins of the Rhabdoviridae and the Paramyxoviridae. PMID:19906936

A structural role for the PHP domain in E. coli DNA polymerase III.

Science.gov (United States)

Barros, Tiago; Guenther, Joel; Kelch, Brian; Anaya, Jordan; Prabhakar, Arjun; O'Donnell, Mike; Kuriyan, John; Lamers, Meindert H

2013-05-14

In addition to the core catalytic machinery, bacterial replicative DNA polymerases contain a Polymerase and Histidinol Phosphatase (PHP) domain whose function is not entirely understood. The PHP domains of some bacterial replicases are active metal-dependent nucleases that may play a role in proofreading. In E. coli DNA polymerase III, however, the PHP domain has lost several metal-coordinating residues and is likely to be catalytically inactive. Genomic searches show that the loss of metal-coordinating residues in polymerase PHP domains is likely to have coevolved with the presence of a separate proofreading exonuclease that works with the polymerase. Although the E. coli Pol III PHP domain has lost metal-coordinating residues, the structure of the domain has been conserved to a remarkable degree when compared to that of metal-binding PHP domains. This is demonstrated by our ability to restore metal binding with only three point mutations, as confirmed by the metal-bound crystal structure of this mutant determined at 2.9 Å resolution. We also show that Pol III, a large multi-domain protein, unfolds cooperatively and that mutations in the degenerate metal-binding site of the PHP domain decrease the overall stability of Pol III and reduce its activity. While the presence of a PHP domain in replicative bacterial polymerases is strictly conserved, its ability to coordinate metals and to perform proofreading exonuclease activity is not, suggesting additional non-enzymatic roles for the domain. Our results show that the PHP domain is a major structural element in Pol III and its integrity modulates both the stability and activity of the polymerase.

Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

International Nuclear Information System (INIS)

Tong, Junsen; Yang, Huiseon; Eom, Soo Hyun; Chun, ChangJu; Im, Young Jun

2014-01-01

Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domain of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering

Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

Energy Technology Data Exchange (ETDEWEB)

Tong, Junsen; Yang, Huiseon [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Eom, Soo Hyun [School of Life Sciences, Steitz Center for Structural Biology, and Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Chun, ChangJu, E-mail: cchun1130@jnu.ac.kr [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Im, Young Jun, E-mail: imyoungjun@jnu.ac.kr [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

2014-09-12

Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domain of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering.

Structure of PIN-domain protein PH0500 from Pyrococcus horikoshii

International Nuclear Information System (INIS)

Jeyakanthan, Jeyaraman; Inagaki, Eiji; Kuroishi, Chizu; Tahirov, Tahir H.

2005-01-01

The structure of P. horikoshii OT3 protein PH0500 was determined by the multiple anomalous dispersion method and refined in two crystal forms. The protein is a dimer and has a PIN-domain fold. The Pyrococcus horikoshii OT3 protein PH0500 is highly conserved within the Pyrococcus genus of hyperthermophilic archaea and shows low amino-acid sequence similarity with a family of PIN-domain proteins. The protein has been expressed, purified and crystallized in two crystal forms: PH0500-I and PH0500-II. The structure was determined at 2.0 Å by the multiple anomalous dispersion method using a selenomethionyl derivative of crystal form PH0500-I (PH0500-I-Se). The structure of PH0500-I has been refined at 1.75 Å resolution to an R factor of 20.9% and the structure of PH0500-II has been refined at 2.0 Å resolution to an R factor of 23.4%. In both crystal forms as well as in solution the molecule appears to be a dimer. Searches of the databases for protein-fold similarities confirmed that the PH0500 protein is a PIN-domain protein with possible exonuclease activity and involvement in DNA or RNA editing

Nonlinear time-domain soil–structure interaction analysis of embedded reactor structures subjected to earthquake loads

Energy Technology Data Exchange (ETDEWEB)

Solberg, Jerome M., E-mail: solberg2@llnl.gov [Methods Development Group, Lawrence Livermore Nat’l Lab, P.O. Box 808, Mailstop L-125, Livermore, CA 94550 (United States); Hossain, Quazi, E-mail: hossain1@llnl.gov [Structural and Applied Mechanics Group, Lawrence Livermore Nat’l Lab, P.O. Box 808, Mailstop L-129, Livermore, CA 94550 (United States); Mseis, George, E-mail: george.mseis@gmail.com [Structural and Applied Mechanics Group, Lawrence Livermore Nat’l Lab, P.O. Box 808, Mailstop L-129, Livermore, CA 94550 (United States)

2016-08-01

Highlights: • Derived modified version of Bielak’s SSI method for nonlinear time-domain analysis. • Utilized a Ramberg–Osgood material with parameters that can be fit to EPRI data. • Matched vertically propagating shear wave results from CARES. • Applied this technique to a representative SMR, compared well with SASSI. • The technique is extensible to other material models and nonlinear effects. - Abstract: A generalized time-domain method for soil–structure interaction analysis is developed, based upon an extension of the work of the domain reduction method of Bielak et al. The methodology is combined with the use of a simple hysteretic soil model based upon the Ramberg–Osgood formulation and applied to a notional Small Modular Reactor. These benchmark results compare well (with some caveats) with those obtained by using the industry-standard frequency-domain code SASSI. The methodology provides a path forward for investigation of other sources of nonlinearity, including those associated with the use of more physically-realistic material models incorporating pore-pressure effects, gap opening/closing, the effect of nonlinear structural elements, and 3D seismic inputs.

Structure and evolution of N-domains in AAA metalloproteases.

Science.gov (United States)

Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

2015-02-27

Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

Structure of the human histone chaperone FACT Spt16 N-terminal domain

Energy Technology Data Exchange (ETDEWEB)

Marcianò, G.; Huang, D. T., E-mail: d.huang@beatson.gla.ac.uk [Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland (United Kingdom)

2016-01-22

The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.

Structure of the human histone chaperone FACT Spt16 N-terminal domain

International Nuclear Information System (INIS)

Marcianò, G.; Huang, D. T.

2016-01-01

The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding

Radiation-damage-assisted ferroelectric domain structuring in magnesium-doped lithium niobate

Science.gov (United States)

Jentjens, L.; Peithmann, K.; Maier, K.; Steigerwald, H.; Jungk, T.

2009-06-01

Irradiation of 5% magnesium-doped lithium niobate crystals (LiNbO3:Mg) with high-energy, low-mass 3He ions, which are transmitted through the crystal, changes the domain reversal properties of the material. This enables easier domain engineering compared to non-irradiated material and assists the formation of small-sized periodically poled domains in LiNbO3:Mg. Periodic domain structures exhibiting a width of ≈520 nm are obtained in radiation-damaged sections of the crystals. The ferroelectric poling behavior between irradiated and non-treated material is compared.

Structure of Pseudoknot PK26 Shows 3D Domain Swapping in an RNA

Science.gov (United States)

Lietzke, Susan E; Barnes, Cindy L.

1998-01-01

3D domain swapping provides a facile pathway for the evolution of oligomeric proteins and allosteric mechanisms and a means for using monomer-oligomer equilibria to regulate biological activity. The term "3D domain swapping" describes the exchange of identical domains between two protein monomers to create an oligomer. 3D domain swapping has, so far, only been recognized in proteins. In this study, the structure of the pseudoknot PK26 is reported and it is a clear example of 3D domain swapping in RNA. PK26 was chosen for study because RNA pseudoknots are required structures in several biological processes and they arise frequently in in vitro selection experiments directed against protein targets. PK26 specifically inhibits HIV-1 reverse transcriptase with nanomolar affinity. We have now determined the 3.1 A resolution crystal structure of PK26 and find that it forms a 3D domain swapped dimer. PK26 shows extensive base pairing between and within strands. Formation of the dimer requires the linker region between the pseudoknot folds to adopt a unique conformation that allows a base within a helical stem to skip one base in the stacking register. Rearrangement of the linker would permit a monomeric pseudoknot to form. This structure shows how RNA can use 3D domain swapping to build large scale oligomers like the putative hexamer in the packaging RNA of bacteriophage Phi29.

Three-dimensional structure of N-terminal domain of DnaB helicase and helicase-primase interactions in Helicobacter pylori.

Directory of Open Access Journals (Sweden)

Tara Kashav

2009-10-01

Full Text Available Replication initiation is a crucial step in genome duplication and homohexameric DnaB helicase plays a central role in the replication initiation process by unwinding the duplex DNA and interacting with several other proteins during the process of replication. N-terminal domain of DnaB is critical for helicase activity and for DnaG primase interactions. We present here the crystal structure of the N-terminal domain (NTD of H. pylori DnaB (HpDnaB helicase at 2.2 A resolution and compare the structural differences among helicases and correlate with the functional differences. The structural details of NTD suggest that the linker region between NTD and C-terminal helicase domain plays a vital role in accurate assembly of NTD dimers. The sequence analysis of the linker regions from several helicases reveals that they should form four helix bundles. We also report the characterization of H. pylori DnaG primase and study the helicase-primase interactions, where HpDnaG primase stimulates DNA unwinding activity of HpDnaB suggesting presence of helicase-primase cohort at the replication fork. The protein-protein interaction study of C-terminal domain of primase and different deletion constructs of helicase suggests that linker is essential for proper conformation of NTD to interact strongly with HpDnaG. The surface charge distribution on the primase binding surface of NTDs of various helicases suggests that DnaB-DnaG interaction and stability of the complex is most probably charge dependent. Structure of the linker and helicase-primase interactions indicate that HpDnaB differs greatly from E.coli DnaB despite both belong to gram negative bacteria.

Structure and hydration of membranes embedded with voltage-sensing domains.

Science.gov (United States)

Krepkiy, Dmitriy; Mihailescu, Mihaela; Freites, J Alfredo; Schow, Eric V; Worcester, David L; Gawrisch, Klaus; Tobias, Douglas J; White, Stephen H; Swartz, Kenton J

2009-11-26

Despite the growing number of atomic-resolution membrane protein structures, direct structural information about proteins in their native membrane environment is scarce. This problem is particularly relevant in the case of the highly charged S1-S4 voltage-sensing domains responsible for nerve impulses, where interactions with the lipid bilayer are critical for the function of voltage-activated ion channels. Here we use neutron diffraction, solid-state nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations to investigate the structure and hydration of bilayer membranes containing S1-S4 voltage-sensing domains. Our results show that voltage sensors adopt transmembrane orientations and cause a modest reshaping of the surrounding lipid bilayer, and that water molecules intimately interact with the protein within the membrane. These structural findings indicate that voltage sensors have evolved to interact with the lipid membrane while keeping energetic and structural perturbations to a minimum, and that water penetrates the membrane, to hydrate charged residues and shape the transmembrane electric field.

Structural predictions for Correlated Electron Materials Using the Functional Dynamical Mean Field Theory Approach

Science.gov (United States)

Haule, Kristjan

2018-04-01

The Dynamical Mean Field Theory (DMFT) in combination with the band structure methods has been able to address reach physics of correlated materials, such as the fluctuating local moments, spin and orbital fluctuations, atomic multiplet physics and band formation on equal footing. Recently it is getting increasingly recognized that more predictive ab-initio theory of correlated systems needs to also address the feedback effect of the correlated electronic structure on the ionic positions, as the metal-insulator transition is almost always accompanied with considerable structural distortions. We will review recently developed extension of merger between the Density Functional Theory (DFT) and DMFT method, dubbed DFT+ embedded DMFT (DFT+eDMFT), whichsuccessfully addresses this challenge. It is based on the stationary Luttinger-Ward functional to minimize the numerical error, it subtracts the exact double-counting of DFT and DMFT, and implements self-consistent forces on all atoms in the unit cell. In a few examples, we will also show how the method elucidated the important feedback effect of correlations on crystal structure in rare earth nickelates to explain the mechanism of the metal-insulator transition. The method showed that such feedback effect is also essential to understand the dynamic stability of the high-temperature body-centered cubic phase of elemental iron, and in particular it predicted strong enhancement of the electron-phonon coupling over DFT values in FeSe, which was very recently verified by pioneering time-domain experiment.

Particle correlations in the recombination model associated with modified Kuti-Weisskopf structure functions

International Nuclear Information System (INIS)

Takasugi, E.; Tata, X.

1982-01-01

The recombination model associated with modified Kuti-Weisskopf multiquark structure functions is used to analyze particle production by hadronic collisions. The justification of the use of the impulse approximation in these processes and the universal nature of the recombination process are discussed. Single-meson inclusive production in the fragmentation domains of the proton, the pion, and the kaon is used as an input to determine the primitive structure functions. Our parameter-free predictions for low-p/sub T/ multimeson and associated meson-baryon inclusive production are found to be in good agreement with a large amount of recently obtained correlation data. It is pointed out, however, that reactions involving multivalence recombination fall outside the scope of present considerations

Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies.

Directory of Open Access Journals (Sweden)

Shannon E Hill

Full Text Available Olfactomedin (OLF domains are found within extracellular, multidomain proteins in numerous tissues of multicellular organisms. Even though these proteins have been implicated in human disorders ranging from cancers to attention deficit disorder to glaucoma, little is known about their structure(s and function(s. Here we biophysically, biochemically, and structurally characterize OLF domains from H. sapiens olfactomedin-1 (npoh-OLF, also called noelin, pancortin, OLFM1, and hOlfA, and M. musculus gliomedin (glio-OLF, also called collomin, collmin, and CRG-L2, and compare them with available structures of myocilin (myoc-OLF recently reported by us and R. norvegicus glio-OLF and M. musculus latrophilin-3 (lat3-OLF by others. Although the five-bladed β-propeller architecture remains unchanged, numerous physicochemical characteristics differ among these OLF domains. First, npoh-OLF and glio-OLF exhibit prominent, yet distinct, positive surface charges and copurify with polynucleotides. Second, whereas npoh-OLF and myoc-OLF exhibit thermal stabilities typical of human proteins near 55°C, and most myoc-OLF variants are destabilized and highly prone to aggregation, glio-OLF is nearly 20°C more stable and significantly more resistant to chemical denaturation. Phylogenetically, glio-OLF is most similar to primitive OLFs, and structurally, glio-OLF is missing distinguishing features seen in OLFs such as the disulfide bond formed by N- and C- terminal cysteines, the sequestered Ca2+ ion within the propeller central hydrophilic cavity, and a key loop-stabilizing cation-π interaction on the top face of npoh-OLF and myoc-OLF. While deciphering the explicit biological functions, ligands, and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, we used structural insights gained here to generate a new antibody selective for myoc-OLF over npoh-OLF and glio-OLF as a first step in overcoming the impasse in

Both Epistasis and Diversifying Selection Drive the Structural Evolution of the Ebola Virus Glycoprotein Mucin-Like Domain.

Science.gov (United States)

Ibeh, Neke; Nshogozabahizi, Jean Claude; Aris-Brosou, Stéphane

2016-06-01

Throughout the last 3 decades, Ebola virus (EBOV) outbreaks have been confined to isolated areas within Central Africa; however, the 2014 variant reached unprecedented transmission and mortality rates. While the outbreak was still under way, it was reported that the variant leading up to this outbreak evolved faster than previous EBOV variants, but evidence for diversifying selection was undetermined. Here, we test this selection hypothesis and show that while previous EBOV outbreaks were preceded by bursts of diversification, evidence for site-specific diversifying selection during the emergence of the 2014 EBOV clade is weak. However, we show strong evidence supporting an interplay between selection and correlated evolution (epistasis), particularly in the mucin-like domain (MLD) of the EBOV glycoprotein. By reconstructing ancestral structures of the MLD, we further propose a structural mechanism explaining how the substitutions that accumulated between 1918 and 1969 distorted the MLD, while more recent epistatic substitutions restored part of the structure, with the most recent substitution being adaptive. We suggest that it is this complex interplay between weak selection, epistasis, and structural constraints that has shaped the evolution of the 2014 EBOV variant. The role that selection plays in the emergence of viral epidemics remains debated, particularly in the context of the 2014 EBOV outbreak. Most critically, should such evidence exist, it is generally unclear how this relates to function and increased virulence. Here, we show that the viral lineage leading up to the 2014 outbreak underwent a complex interplay between selection and correlated evolution (epistasis) in a protein region that is critical for immune evasion. We then reconstructed the three-dimensional structure of this domain and showed that the initial mutations in this lineage deformed the structure, while subsequent mutations restored part of the structure. Along this mutational path, the

Crystal structure studies of NADP{sup +} dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain

Energy Technology Data Exchange (ETDEWEB)

Kumar, S.M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Pampa, K.J. [Department of Studies in Microbiology, University of Mysore, Mysore 570 006 (India); Manjula, M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Abdoh, M.M.M. [Department of Physics, Faculty of Science, An-Najah National University, Nablus, West Bank, Palestine (Country Unknown); Kunishima, Naoki [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, Hyogo 679-5148 (Japan); Lokanath, N.K., E-mail: lokanath@physics.uni-mysore.ac.in [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India)

2014-06-20

Highlights: • We determined the structure of isocitrate dehydrogenase with citrate and cofactor. • The structure reveals a unique novel terminal domain involved in dimerization. • Clasp domain shows significant difference, and catalytic residues are conserved. • Oligomerization of the enzyme is quantized with subunit-subunit interactions. • Novel domain of this enzyme is classified as subfamily of the type IV. - Abstract: NADP{sup +} dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP{sup +} was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH’s. And, small domain and clasp domain showing significant differences when compared to other IDH’s of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH’s. Also, helices/beta sheets are absent in the small domain, when compared to other IDH’s of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit–subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.

Color centers in KCN: a structural analysis of crystalline domains

International Nuclear Information System (INIS)

Carmo, L.C.S. do.

1976-03-01

Pure singlecrystals of KCN exposed to X-rays showed several color centers detected by EPR. The F center was identified through the correlation of its optical absorption band which satisfies the Ivey law for the KCN lattice parameter and the EPR spectrum typical of a center in an anionic site. Two other color centers were identified: N - 2 and HCN - . Two centers assigned to hydrogen atoms have their models proposed: U 2 and U 3 centers. Two other centers remain unidentified: an anionic and an extrinsic centers. The orthorhombic character of the N - 2 center EPR parameters allowed an structural analysis of the crystal line domains in the orthorhombic phase. The optical absorption spectrum of the HCN - center in KCl matrix was investigated and showed a set of resolved bands with a constant energy splitting; this splitting was associated to a vibrational mode of the excited state of this molecular ion. (author) [pt

Crystal Structure of the Marburg Virus VP35 Oligomerization Domain

Energy Technology Data Exchange (ETDEWEB)

Bruhn, Jessica F.; Kirchdoerfer, Robert N.; Urata, Sarah M.; Li, Sheng; Tickle, Ian J.; Bricogne, Gérard; Saphire, Erica Ollmann (Scripps); (Globel Phasing); (UCSD)

2016-11-09

Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (generaMarburgvirusandEbolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOV VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV.

IMPORTANCEMarburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the

Soil-structure interaction analysis of NPP containments: substructure and frequency domain methods

International Nuclear Information System (INIS)

Venancio-Filho, F.; Almeida, M.C.F.; Ferreira, W.G.; De Barros, F.C.P.

1997-01-01

Substructure and frequency domain methods for soil-structure interaction are addressed in this paper. After a brief description of mathematical models for the soil and of excitation, the equations for dynamic soil-structure interaction are developed for a rigid surface foundation and for an embedded foundation. The equations for the frequency domain analysis of MDOF systems are provided. An example of soil-structure interaction analysis with frequency-dependent soil properties is given and examples of identification of foundation impedance functions and soil properties are presented. (orig.)

Overcoming artificial spatial correlations in simulations of superstructure domain growth with parallel Monte Carlo algorithms

International Nuclear Information System (INIS)

Schleier, W.; Besold, G.; Heinz, K.

1992-01-01

The authors study the applicability of parallelized/vectorized Monte Carlo (MC) algorithms to the simulation of domain growth in two-dimensional lattice gas models undergoing an ordering process after a rapid quench below an order-disorder transition temperature. As examples they consider models with 2 x 1 and c(2 x 2) equilibrium superstructures on the square and rectangular lattices, respectively. They also study the case of phase separation ('1 x 1' islands) on the square lattice. A generalized parallel checkerboard algorithm for Kawasaki dynamics is shown to give rise to artificial spatial correlations in all three models. However, only if superstructure domains evolve do these correlations modify the kinetics by influencing the nucleation process and result in a reduced growth exponent compared to the value from the conventional heat bath algorithm with random single-site updates. In order to overcome these artificial modifications, two MC algorithms with a reduced degree of parallelism ('hybrid' and 'mask' algorithms, respectively) are presented and applied. As the results indicate, these algorithms are suitable for the simulation of superstructure domain growth on parallel/vector computers. 60 refs., 10 figs., 1 tab

Conduction at domain walls in oxide multiferroics

Science.gov (United States)

Seidel, J.; Martin, L. W.; He, Q.; Zhan, Q.; Chu, Y.-H.; Rother, A.; Hawkridge, M. E.; Maksymovych, P.; Yu, P.; Gajek, M.; Balke, N.; Kalinin, S. V.; Gemming, S.; Wang, F.; Catalan, G.; Scott, J. F.; Spaldin, N. A.; Orenstein, J.; Ramesh, R.

2009-03-01

Domain walls may play an important role in future electronic devices, given their small size as well as the fact that their location can be controlled. Here, we report the observation of room-temperature electronic conductivity at ferroelectric domain walls in the insulating multiferroic BiFeO3. The origin and nature of the observed conductivity are probed using a combination of conductive atomic force microscopy, high-resolution transmission electron microscopy and first-principles density functional computations. Our analyses indicate that the conductivity correlates with structurally driven changes in both the electrostatic potential and the local electronic structure, which shows a decrease in the bandgap at the domain wall. Additionally, we demonstrate the potential for device applications of such conducting nanoscale features.

High-resolution NMR structures of the domains of Saccharomyces cerevisiae Tho1

International Nuclear Information System (INIS)

Jacobsen, Julian O. B.; Allen, Mark D.; Freund, Stefan M. V.; Bycroft, Mark

2016-01-01

In this study, high-resolution structures of both the N-terminal DNA-binding SAP domain and the C-terminal RNA-binding domain of S. cerevisiae Tho1 have been determined. THO is a multi-protein complex involved in the formation of messenger ribonuclear particles (mRNPs) by coupling transcription with mRNA processing and export. THO is thought to be formed from five subunits, Tho2p, Hpr1p, Tex1p, Mft1p and Thp2p, and recent work has determined a low-resolution structure of the complex [Poulsen et al. (2014 ▸), PLoS One, 9, e103470]. A number of additional proteins are thought to be involved in the formation of mRNP in yeast, including Tho1, which has been shown to bind RNA in vitro and is recruited to actively transcribed chromatin in vivo in a THO-complex and RNA-dependent manner. Tho1 is known to contain a SAP domain at the N-terminus, but the ability to suppress the expression defects of the hpr1Δ mutant of THO was shown to reside in the RNA-binding C-terminal region. In this study, high-resolution structures of both the N-terminal DNA-binding SAP domain and C-terminal RNA-binding domain have been determined

High-resolution NMR structures of the domains of Saccharomyces cerevisiae Tho1

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Jacobsen, Julian O. B.; Allen, Mark D.; Freund, Stefan M. V.; Bycroft, Mark, E-mail: mxb@mrc-lmb.cam.ac.uk [MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH (United Kingdom)

2016-05-23

In this study, high-resolution structures of both the N-terminal DNA-binding SAP domain and the C-terminal RNA-binding domain of S. cerevisiae Tho1 have been determined. THO is a multi-protein complex involved in the formation of messenger ribonuclear particles (mRNPs) by coupling transcription with mRNA processing and export. THO is thought to be formed from five subunits, Tho2p, Hpr1p, Tex1p, Mft1p and Thp2p, and recent work has determined a low-resolution structure of the complex [Poulsen et al. (2014 ▸), PLoS One, 9, e103470]. A number of additional proteins are thought to be involved in the formation of mRNP in yeast, including Tho1, which has been shown to bind RNA in vitro and is recruited to actively transcribed chromatin in vivo in a THO-complex and RNA-dependent manner. Tho1 is known to contain a SAP domain at the N-terminus, but the ability to suppress the expression defects of the hpr1Δ mutant of THO was shown to reside in the RNA-binding C-terminal region. In this study, high-resolution structures of both the N-terminal DNA-binding SAP domain and C-terminal RNA-binding domain have been determined.

The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.

Science.gov (United States)

Fedoroff, Oleg Y; Townson, Sharon A; Golovanov, Alexander P; Baron, Martin; Avis, Johanna M

2004-08-13

WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.

Structure and correlating variables of attitudes of students, future helping professionals, towards persons with hearing impairments

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Glintić Milica

2014-01-01

Full Text Available The aim of this study was to explore the structure and the correlates of students attitudes towards persons with hearing impairments. The sample consisted of 103 first year students of The Faculty of Special Education and Rehabilitation (F-93; M-10, divisions Prevention and treatment of conduct disorders and Speech therapy. These attitudes were assessed by The revised version of Multidimensional Attitudes Scale Toward Persons With Disabilities, Empathy by Empathy Quotient, dimensions of personality by The Big Five Inventory, the attachment by Experiences in Close Relationships Scale, the motivation for studying the Faculty of Special Education and Rehabilitation by the scale assembled for this research. It was found that in the domain of basic dimensions of personality only tendency to collaborate with others negatively correlates with absence of pro-social thoughts (-0.204, scale of anxiety in close relationships, in attachment domain, positively correlates with inhibiting thoughts and feelings (0.220, while the empathy quotient negatively correlates with the absence of pro-social thoughts (-0.226. The motivation for studying Faculty of Special Education and Rehabilitation was not associated with components of the attitude towards people with hearing impairment. Future researches should try to identify predictors of negative emotional and behavioral which lead to ignoring and rejecting of persons with disability.

Shapes of isolated domains and field induced evolution of regular and random 2D domain structures in LiNbO3 and LiTaO3

International Nuclear Information System (INIS)

Chernykh, A.; Shur, V.; Nikolaeva, E.; Shishkin, E.; Shur, A.; Terabe, K.; Kurimura, S.; Kitamura, K.; Gallo, K.

2005-01-01

The variety of the shapes of isolated domains, revealed in congruent and stoichiometric LiTaO 3 and LiNbO 3 by chemical etching and visualized by optical and scanning probe microscopy, was obtained by computer simulation. The kinetic nature of the domain shape was clearly demonstrated. The kinetics of domain structure with the dominance of the growth of the steps formed at the domain walls as a result of domain merging was investigated experimentally in slightly distorted artificial regular two-dimensional (2D) hexagonal domain structure and random natural one. The artificial structure has been realized in congruent LiNbO 3 by 2D electrode pattern produced by photolithography. The polarization reversal in congruent LiTaO 3 was investigated as an example of natural domain growth limited by merging. The switching process defined by domain merging was studied by computer simulation. The crucial dependence of the switching kinetics on the nuclei concentration has been revealed

Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications

Science.gov (United States)

Cvicek, Vaclav; Goddard, William A.; Abrol, Ravinder

2016-01-01

The understanding of G-protein coupled receptors (GPCRs) is undergoing a revolution due to increased information about their signaling and the experimental determination of structures for more than 25 receptors. The availability of at least one receptor structure for each of the GPCR classes, well separated in sequence space, enables an integrated superfamily-wide analysis to identify signatures involving the role of conserved residues, conserved contacts, and downstream signaling in the context of receptor structures. In this study, we align the transmembrane (TM) domains of all experimental GPCR structures to maximize the conserved inter-helical contacts. The resulting superfamily-wide GpcR Sequence-Structure (GRoSS) alignment of the TM domains for all human GPCR sequences is sufficient to generate a phylogenetic tree that correctly distinguishes all different GPCR classes, suggesting that the class-level differences in the GPCR superfamily are encoded at least partly in the TM domains. The inter-helical contacts conserved across all GPCR classes describe the evolutionarily conserved GPCR structural fold. The corresponding structural alignment of the inactive and active conformations, available for a few GPCRs, identifies activation hot-spot residues in the TM domains that get rewired upon activation. Many GPCR mutations, known to alter receptor signaling and cause disease, are located at these conserved contact and activation hot-spot residue positions. The GRoSS alignment places the chemosensory receptor subfamilies for bitter taste (TAS2R) and pheromones (Vomeronasal, VN1R) in the rhodopsin family, known to contain the chemosensory olfactory receptor subfamily. The GRoSS alignment also enables the quantification of the structural variability in the TM regions of experimental structures, useful for homology modeling and structure prediction of receptors. Furthermore, this alignment identifies structurally and functionally important residues in all human GPCRs

Correlations between physical activity and neurocognitive domain functions in patients with schizophrenia: a cross-sectional study.

Science.gov (United States)

Kurebayashi, Yusuke; Otaki, Junichi

2017-01-05

Neurocognitive dysfunction is a critical target symptom of schizophrenia treatment. A positive correlation between physical activity level and neurocognitive function has been reported in healthy individuals, but it is unclear whether such a correlation exists in patients with schizophrenia and whether the relationship is different according to inpatients or outpatients. This study aimed to examine the differences in the correlations between physical activity and multiple neurocognitive domains in inpatients and outpatients with schizophrenia and obtain suggestions for further study to facilitate this field. Twenty-nine patients with schizophrenia were examined (16 inpatients and 13 outpatients, 56.0 ± 11.4 years of age). Current symptoms were assessed using the Positive and Negative Symptom Scale and neurocognitive functions using Cognitrax, which yields a composite neurocognitive index (NCI) and 11 domain scores. After testing, participants wore an HJA-750C accelerometer for one week to measure physical activity levels and durations. Partial correlation analyses were performed between exercise and cognitive parameters. In the outpatient group, higher physical activity was associated with faster Motor and Psychomotor Speeds in outpatients. However, higher physical activity was associated with lower overall NCI, Attention score, and Memory scores in inpatients. Although higher physical activity was associated with better neurocognitive functions of outpatients, in inpatients with non-remitted schizophrenia, higher physical activity was associated with worsening of several cognitive domains. In a future study examining the relationship between physical activity and neurocognitive function for facilitating this research field, separation between inpatients and outpatients are needed because the relationship is different between inpatients and outpatients.

Structure of the C-terminal heme-binding domain of THAP domain containing protein 4 from Homo sapiens

Energy Technology Data Exchange (ETDEWEB)

Bianchetti, Christopher M.; Bingman, Craig A.; Phillips, Jr., George N. (UW)

2012-03-15

The thanatos (the Greek god of death)-associated protein (THAP) domain is a sequence-specific DNA-binding domain that contains a C2-CH (Cys-Xaa{sub 2-4}-Cys-Xaa{sub 35-50}-Cys-Xaa{sub 2}-His) zinc finger that is similar to the DNA domain of the P element transposase from Drosophila. THAP-containing proteins have been observed in the proteome of humans, pigs, cows, chickens, zebrafish, Drosophila, C. elegans, and Xenopus. To date, there are no known THAP domain proteins in plants, yeast, or bacteria. There are 12 identified human THAP domain-containing proteins (THAP0-11). In all human THAP protein, the THAP domain is located at the N-terminus and is {approx}90 residues in length. Although all of the human THAP-containing proteins have a homologous N-terminus, there is extensive variation in both the predicted structure and length of the remaining protein. Even though the exact function of these THAP proteins is not well defined, there is evidence that they play a role in cell proliferation, apoptosis, cell cycle modulation, chromatin modification, and transcriptional regulation. THAP-containing proteins have also been implicated in a number of human disease states including heart disease, neurological defects, and several types of cancers. Human THAP4 is a 577-residue protein of unknown function that is proposed to bind DNA in a sequence-specific manner similar to THAP1 and has been found to be upregulated in response to heat shock. THAP4 is expressed in a relatively uniform manner in a broad range of tissues and appears to be upregulated in lymphoma cells and highly expressed in heart cells. The C-terminal domain of THAP4 (residues 415-577), designated here as cTHAP4, is evolutionarily conserved and is observed in all known THAP4 orthologs. Several single-domain proteins lacking a THAP domain are found in plants and bacteria and show significant levels of homology to cTHAP4. It appears that cTHAP4 belongs to a large class of proteins that have yet to be fully

Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter

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Robert Schulz

2015-01-01

Full Text Available As active part of the major efflux system in E. coli bacteria, AcrB is responsible for the uptake and pumping of toxic substrates from the periplasm toward the extracellular space. In combination with the channel protein TolC and membrane fusion protein AcrA, this efflux pump is able to help the bacterium to survive different kinds of noxious compounds. With the present study we intend to enhance the understanding of the interactions between the domains and monomers, for example, the transduction of mechanical energy from the transmembrane domain into the porter domain, correlated motions of different subdomains within monomers, and cooperative effects between monomers. To this end, targeted molecular dynamics simulations have been employed either steering the whole protein complex or specific parts thereof. By forcing only parts of the complex towards specific conformational states, the risk for transient artificial conformations during the simulations is reduced. Distinct cooperative effects between the monomers in AcrB have been observed. Possible allosteric couplings have been identified providing microscopic insights that might be exploited to design more efficient inhibitors of efflux systems.

Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain.

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The Quyen Nguyen

Full Text Available Kinesin1 plays a major role in neuronal transport by recruiting many different cargos through its kinesin light chain (KLC. Various structurally unrelated cargos interact with the conserved tetratricopeptide repeat (TPR domain of KLC. The N-terminal capping helix of the TPR domain exhibits an atypical sequence and structural features that may contribute to the versatility of the TPR domain to bind different cargos. We determined crystal structures of the TPR domain of both KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix exhibits two distinct and defined orientations relative to the rest of the TPR domain. Such a difference in orientation gives rise, at the N-terminal part of the groove, to the formation of one hydrophobic pocket, as well as to electrostatic variations at the groove surface. We present a comprehensive structural analysis of available KLC1/2-TPR domain structures that highlights that ligand binding into the groove can be specific of one or the other N-terminal capping helix orientations. Further, structural analysis reveals that the N-terminal capping helix is always involved in crystal packing contacts, especially in a TPR1:TPR1' contact which highlights its propensity to be a protein-protein interaction site. Together, these results underline that the structural plasticity of the N-terminal capping helix might represent a structural determinant for TPR domain structural versatility in cargo binding.

Building and Using Object-Oriented Frameworks for Semi-Structures Domains: The Sales Promotion Domain as Example

NARCIS (Netherlands)

A. Dalebout; J. van Hillegersberg (Jos); B. Wierenga (Berend)

1998-01-01

textabstractObject-oriented (00) frameworks are considered an important step forward in developing software applications efficiently. Success of frameworks has however predominantly been limited to structured domains.This paper describes a method for developing 00 domainframeworks for

Structures of the Porphyromonas gingivalis OxyR regulatory domain explain differences in expression of the OxyR regulon in Escherichia coli and P. gingivalis

Energy Technology Data Exchange (ETDEWEB)

Svintradze, David V. [Virginia Commonwealth University, Richmond, VA 23298-0566 (United States); Virginia Commonwealth University, Richmond, VA 23219-1540 (United States); Peterson, Darrell L. [Virginia Commonwealth University, Richmond, VA 23219-1540 (United States); Virginia Commonwealth University, Richmond, VA 23298-0614 (United States); Collazo-Santiago, Evys A.; Lewis, Janina P. [Virginia Commonwealth University, Richmond, VA 23298-0566 (United States); Wright, H. Tonie, E-mail: xrdproc@vcu.edu [Virginia Commonwealth University, Richmond, VA 23219-1540 (United States); Virginia Commonwealth University, Richmond, VA 23298-0614 (United States); Virginia Commonwealth University, Richmond, VA 23298-0566 (United States)

2013-10-01

Differences in OxyR regulated expression of oxidative stress genes between Escherichia coli and Porphyromonas gingivalis are explained by very minor differences in structure and amino-acid sequence of the respective oxidized and reduced OxyR regulatory domains. These differences affect OxyR quaternary structures and are predicted from model building of full length OxyR–DNA complexes to confer distinct modes of DNA binding on this transcriptional regulator. OxyR transcriptionally regulates Escherichia coli oxidative stress response genes through a reversibly reducible cysteine disulfide biosensor of cellular redox status. Structural changes induced by redox changes in these cysteines are conformationally transmitted to the dimer subunit interfaces, which alters dimer and tetramer interactions with DNA. In contrast to E. coli OxyR regulatory-domain structures, crystal structures of Porphyromonas gingivalis OxyR regulatory domains show minimal differences in dimer configuration on changes in cysteine disulfide redox status. This locked configuration of the P. gingivalis OxyR regulatory-domain dimer closely resembles the oxidized (activating) form of the E. coli OxyR regulatory-domain dimer. It correlates with the observed constitutive activation of some oxidative stress genes in P. gingivalis and is attributable to a single amino-acid insertion in P. gingivalis OxyR relative to E. coli OxyR. Modelling of full-length P. gingivalis, E. coli and Neisseria meningitidis OxyR–DNA complexes predicts different modes of DNA binding for the reduced and oxidized forms of each.

Structures of the Porphyromonas gingivalis OxyR regulatory domain explain differences in expression of the OxyR regulon in Escherichia coli and P. gingivalis

International Nuclear Information System (INIS)

Svintradze, David V.; Peterson, Darrell L.; Collazo-Santiago, Evys A.; Lewis, Janina P.; Wright, H. Tonie

2013-01-01

Differences in OxyR regulated expression of oxidative stress genes between Escherichia coli and Porphyromonas gingivalis are explained by very minor differences in structure and amino-acid sequence of the respective oxidized and reduced OxyR regulatory domains. These differences affect OxyR quaternary structures and are predicted from model building of full length OxyR–DNA complexes to confer distinct modes of DNA binding on this transcriptional regulator. OxyR transcriptionally regulates Escherichia coli oxidative stress response genes through a reversibly reducible cysteine disulfide biosensor of cellular redox status. Structural changes induced by redox changes in these cysteines are conformationally transmitted to the dimer subunit interfaces, which alters dimer and tetramer interactions with DNA. In contrast to E. coli OxyR regulatory-domain structures, crystal structures of Porphyromonas gingivalis OxyR regulatory domains show minimal differences in dimer configuration on changes in cysteine disulfide redox status. This locked configuration of the P. gingivalis OxyR regulatory-domain dimer closely resembles the oxidized (activating) form of the E. coli OxyR regulatory-domain dimer. It correlates with the observed constitutive activation of some oxidative stress genes in P. gingivalis and is attributable to a single amino-acid insertion in P. gingivalis OxyR relative to E. coli OxyR. Modelling of full-length P. gingivalis, E. coli and Neisseria meningitidis OxyR–DNA complexes predicts different modes of DNA binding for the reduced and oxidized forms of each

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

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Zomaya Albert Y

2006-12-01

Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

Structure determination and analysis of a haemolytic gingipain adhesin domain from Porphyromonas gingivalis

Energy Technology Data Exchange (ETDEWEB)

Li, N.; Yun, P.; Nadkarni, M.A.; Ghadikolaee, N.B.; Nguyen, K.A.; Lee, M.; Hunter, N.; Collyer, C.A. (Sydney)

2010-08-27

Porphyromonas gingivalis is an obligately anaerobic bacterium recognized as an aetiological agent of adult periodontitis. P. gingivalis produces cysteine proteinases, the gingipains. The crystal structure of a domain within the haemagglutinin region of the lysine gingipain (Kgp) is reported here. The domain was named K2 as it is the second of three homologous structural modules in Kgp. The K2 domain structure is a 'jelly-roll' fold with two anti-parallel {beta}-sheets. This fold topology is shared with adhesive domains from functionally diverse receptors such as MAM domains, ephrin receptor ligand binding domains and a number of carbohydrate binding modules. Possible functions of K2 were investigated. K2 induced haemolysis of erythrocytes in a dose-dependent manner that was augmented by the blocking of anion transport. Further, cysteine-activated arginine gingipain RgpB, which degrades glycophorin A, sensitized erythrocytes to the haemolytic effect of K2. Cleaved K2, similar to that found in extracted Kgp, lacks the haemolytic activity indicating that autolysis of Kgp may be a staged process which is artificially enhanced by extraction of the protein. The data indicate a functional role for K2 in the integrated capacity conferred by Kgp to enable the porphyrin auxotroph P. gingivalis to capture essential haem from erythrocytes.

Domain morphology controlled crystal habits in PbTiO{sub 3} nanocrystals

Energy Technology Data Exchange (ETDEWEB)

Dudhe, C.M., E-mail: chandraguptadudhe@gmail.com; Khambadkar, S.J.

2015-11-05

Various crystal habits and associated domain structures in PbTiO{sub 3} nanocrystals synthesized by a modified sol–gel method have been studied. Structural and morphological characterizations of synthesized nanoparticles have been done by X-ray diffraction (XRD) and transmission electron microscopy (TEM). It was found from the -z coordinates of O{sub 1} and O{sub 2} that the Ti–O{sub 6} octahedra were distorted slightly, favorable for the ferroelectric nature. TEM images show butterfly like, plate like, irregular sphere like and oval-shaped habits of the nanocrystals. 90° and 180° domain structures in these crystal habits were explored from their morphologies and appearance in the field of views. The mutual association between the crystal habit and the direction spontaneous polarization P{sub s} due to domain structures was explored. Domain wall energies of 90° and 180° domains were also estimated from the kinetic process of domain nucleation. - Highlights: • Various crystal habits of PbTiO{sub 3} nanoparticles were examined by TEM. • 90° and 180° domains were explored in the nanocrystal. • Crystal habits and domain structures were correlated. • Domain wall energies were estimated.

Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

International Nuclear Information System (INIS)

Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

2008-01-01

The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

CATHEDRAL: a fast and effective algorithm to predict folds and domain boundaries from multidomain protein structures.

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Oliver C Redfern

2007-11-01

Full Text Available We present CATHEDRAL, an iterative protocol for determining the location of previously observed protein folds in novel multidomain protein structures. CATHEDRAL builds on the features of a fast secondary-structure-based method (using graph theory to locate known folds within a multidomain context and a residue-based, double-dynamic programming algorithm, which is used to align members of the target fold groups against the query protein structure to identify the closest relative and assign domain boundaries. To increase the fidelity of the assignments, a support vector machine is used to provide an optimal scoring scheme. Once a domain is verified, it is excised, and the search protocol is repeated in an iterative fashion until all recognisable domains have been identified. We have performed an initial benchmark of CATHEDRAL against other publicly available structure comparison methods using a consensus dataset of domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows superior performance in fold recognition and alignment accuracy when compared with many equivalent methods. If a novel multidomain structure contains a known fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For nearly 80% of assigned domains in a manually validated test set, the boundaries were correctly delineated within a tolerance of ten residues. For the remaining cases, previously classified domains were very remotely related to the query chain so that embellishments to the core of the fold caused significant differences in domain sizes and manual refinement of the boundaries was necessary. To put this performance in context, a well-established sequence method based on hidden Markov models was only able to detect 65% of domains, with 33% of the subsequent boundaries assigned within ten residues. Since, on average, 50% of newly determined protein structures contain more than one domain unit, and typically 90% or more of these

Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.

Science.gov (United States)

Argentaro, Anthony; Yang, Ji-Chun; Chapman, Lynda; Kowalczyk, Monika S; Gibbons, Richard J; Higgs, Douglas R; Neuhaus, David; Rhodes, Daniela

2007-07-17

The chromatin-associated protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation associated with alpha-thalassemia. Half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX. This region was named the ATRX-DNMT3-DNMT3L (ADD) domain, based on sequence homology with a family of DNA methyltransferases. Here, we report the solution structure of the ADD domain of ATRX, which consists of an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal alpha-helix that pack together to form a single globular domain. Interestingly, the alpha-helix of the GATA-like finger is exposed and highly basic, suggesting a DNA-binding function for ATRX. The disease-causing mutations fall into two groups: the majority affect buried residues and hence affect the structural integrity of the ADD domain; another group affects a cluster of surface residues, and these are likely to perturb a potential protein interaction site. The effects of individual point mutations on the folding state and stability of the ADD domain correlate well with the levels of mutant ATRX protein in patients, providing insights into the molecular pathophysiology of ATR-X syndrome.

Crystal structure of an EAL domain in complex with reaction product 5'-pGpG.

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Julien Robert-Paganin

Full Text Available FimX is a large multidomain protein containing an EAL domain and involved in twitching motility in Pseudomonas aeruginosa. We present here two crystallographic structures of the EAL domain of FimX (residues 438-686: one of the apo form and the other of a complex with 5'-pGpG, the reaction product of the hydrolysis of c-di-GMP. In both crystal forms, the EAL domains form a dimer delimiting a large cavity encompassing the catalytic pockets. The ligand is trapped in this cavity by its sugar phosphate moiety. We confirmed by NMR that the guanine bases are not involved in the interaction in solution. We solved here the first structure of an EAL domain bound to the reaction product 5'-pGpG. Though isolated FimX EAL domain has a very low catalytic activity, which would not be significant compared to other catalytic EAL domains, the structure with the product of the reaction can provides some hints in the mechanism of hydrolysis of the c-di-GMP by EAL domains.

Crystal structure of an EAL domain in complex with reaction product 5'-pGpG.

Science.gov (United States)

Robert-Paganin, Julien; Nonin-Lecomte, Sylvie; Réty, Stéphane

2012-01-01

FimX is a large multidomain protein containing an EAL domain and involved in twitching motility in Pseudomonas aeruginosa. We present here two crystallographic structures of the EAL domain of FimX (residues 438-686): one of the apo form and the other of a complex with 5'-pGpG, the reaction product of the hydrolysis of c-di-GMP. In both crystal forms, the EAL domains form a dimer delimiting a large cavity encompassing the catalytic pockets. The ligand is trapped in this cavity by its sugar phosphate moiety. We confirmed by NMR that the guanine bases are not involved in the interaction in solution. We solved here the first structure of an EAL domain bound to the reaction product 5'-pGpG. Though isolated FimX EAL domain has a very low catalytic activity, which would not be significant compared to other catalytic EAL domains, the structure with the product of the reaction can provides some hints in the mechanism of hydrolysis of the c-di-GMP by EAL domains.

Changing the cubic ferrimagnetic domain structure in temperature region of spin flip transition

International Nuclear Information System (INIS)

Djuraev, D.R.; Niyazov, L.N.; Saidov, K.S.; Sokolov, B.Yu.

2011-01-01

The transformation of cubic ferrimagnetic Tb 0.2 Y 2.8 Fe 5 O 12 domain structure has been studied by magneto optic method in the temperature region of spontaneous spin flip phase transition (SPT). It has been found that SPT occurs in a finite temperature interval where the coexistence of low- and high- temperature magnetic phase domains has observed. A character of domain structure evolution in temperature region of spin flip essentially depends on the presence of mechanical stresses in crystal. Interpretation of experimental results has been carried out within the framework of SPT theory for a cubic crystal. (authors)

The correlates of preschoolers' compliance with screen recommendations exist across multiple domains.

Science.gov (United States)

Hinkley, Trina; Salmon, Jo; Okely, Anthony D; Crawford, David

2013-09-01

To investigate the individual, social and physical environment correlates of preschool children's compliance with Australian/Canadian and American Academy of Pediatrics (AAP) screen recommendations. An Ecological Model (EM) was used to identify constructs potentially associated with children's screen time. In 2008-2009, parents in Melbourne, Australia, reported their child's screen time and on a range of potential correlates. Children (n = 935; 54% boys, mean age 4.54 ± 0.70 years) were assessed as meeting or not meeting each of the screen recommendations. Logistic regression assessed bivariable and multivariable associations. In total, 15 explanatory variables, across the three domains of the EM were associated with boys' and/or girls' compliance with either Australian/Canadian or AAP recommendations. Correlates varied by sex and recommendation. Maternal television viewing time was the only consistent correlate for both boys' and girls' compliance with both recommendations. No demographic groups were identified as being less likely to comply with screen recommendations. Public health programs should take account of the sex-specific nature of correlates of preschool children's screen time. Preschool children across all demographic groups need support to engage in less screen use. Parents may benefit from education and parenting skills to minimize potentially harmful effects of excessive screen time for their child. Copyright © 2013 Elsevier Inc. All rights reserved.

Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB.

Science.gov (United States)

Zeng, Lei; Kuti, Miklos; Mujtaba, Shiraz; Zhou, Ming-Ming

2014-07-01

The fibroblast growth factor receptor (FGFR) substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2α proteins interact with RTKs through the phosphotyrosine-binding (PTB) domain and transfer signals from the activated receptors to downstream effector proteins. Here, we report the nuclear magnetic resonance structure of the FRS2α PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2α-PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either nonphosphorylated juxtamembrane region of the FGFR, or tyrosine phosphorylated peptides TrkA and TrkB. The new structural insights suggest rational design of selective small molecules through targeting of the two conjunct pockets in the FRS2α PTB domain. © 2014 Wiley Periodicals, Inc.

Restoration the domain structure from magnetic force microscopy image

Science.gov (United States)

Wu, Dongping; Lou, Yuanfu; Wei, Fulin; Wei, Dan

2012-04-01

This contribution gives an approximation method to calculate the stray field of the scanning plane from the magnetic force microscopy (MFM) force gradient image. Before calculation, a Butterworth low-pass filter has been used to remove a part of the noise of the image. The discrete Fourier transform (DFT) method has been used to calculate the magnetic potential of the film surface. It shows that the potential is not correct because the low-frequency noise has been enlarged. The approximation method gives a better result of the potential and proves that the MFM force gradient of the perpendicular component image also gives the perpendicular component of the stray field. Supposing that the distance between the tip and the sample is as small as near zero, the force gradient image also gives the magnetic charge distribution of the film surface. So if the orientation of the film from hysteresis loop is known, then the domain structure of the film can be determined. For perpendicular orientation, the absolution value of the perpendicular component of stray field gives the domain and domain wall position. For in-plane orientation, the absolution value of in-plane component of stray field gives the domain and domain wall position.

Magnetization reversal and domain correlation for a non-collinear and out-of-plane exchange-coupled system

International Nuclear Information System (INIS)

Paul, Amitesh; Paul, N; Mattauch, Stefan

2011-01-01

We have investigated the impact of out-of-plane ferromagnetic (FM) anisotropy (which can be coincident with the direction of unidirectional anisotropy), where antiferromagnetic (AF) anisotropy is along the film plane. This provides a platform for non-collinear exchange coupling in an archetypal exchange coupled system in an unconventional way. We probe the in-plane magnetization by the depth-sensitive vector magnetometry technique. The experimental findings reveal a magnetization reversal (i) that is symmetric for both the branches of the hysteresis loop, (ii) that is characterized by vertically correlated domains associated with a strong transverse component of magnetization and (iii) that remains untrained (suppression of trained state) with field cycling. This scenario has been compared with in-plane magnetization reversal for a conventional in-plane unidirectional anisotropic case in the same system that shows usual asymmetric reversal and training for vertically uncorrelated domains. We explain the above observations for the out-of-plane case in terms of inhomogeneous magnetic states due to competing perpendicular anisotropies that result in non-collinear FM-AF coupling. This study provides direct evidence for the vertical correlation of domains mediated by out-of-plane exchange coupling.

Control systems using modal domain optical fiber sensors for smart structure applications

Science.gov (United States)

Lindner, Douglas K.; Reichard, Karl M.

1991-01-01

Recently, a new class of sensors has emerged for structural control which respond to environmental changes over a significant gauge length; these sensors are called distributed-effect sensors. These sensors can be fabricated with spatially varying sensitivity to the distributed measurand, and can be configured to measure a variety of structural parameters which can not be measured directly using point sensors. Examples of distributed-effect sensors include piezoelectric film, holographic sensors, and modal domain optical fiber sensors. Optical fiber sensors are particularly attractive for smart structure applications because they are flexible, have low mass, and can easily be embedded directly into materials. In this paper we describe the implementation of weighted modal domain optical fiber sensors. The mathematical model of the modal domain optical fiber sensor model is described and used to derive an expression for the sensor sensitivity. The effects of parameter variations on the sensor sensitivity are demonstrated to illustrate methods of spatially varying the sensor sensitivity.

Time-domain soil-structure interaction analysis of nuclear facilities

International Nuclear Information System (INIS)

Coleman, Justin L.; Bolisetti, Chandrakanth; Whittaker, Andrew S.

2016-01-01

The Nuclear Regulatory Commission (NRC) regulation 10 CFR Part 50 Appendix S requires consideration of soil-structure interaction (SSI) in nuclear power plant (NPP) analysis and design. Soil-structure interaction analysis for NPPs is routinely carried out using guidance provided in the ASCE Standard 4-98 titled “Seismic Analysis of Safety-Related Nuclear Structures and Commentary”. This Standard, which is currently under revision, provides guidance on linear seismic soil-structure-interaction (SSI) analysis of nuclear facilities using deterministic and probabilistic methods. A new appendix has been added to the forthcoming edition of ASCE Standard 4 to provide guidance for time-domain, nonlinear SSI (NLSSI) analysis. Nonlinear SSI analysis will be needed to simulate material nonlinearity in soil and/or structure, static and dynamic soil pressure effects on deeply embedded structures, local soil failure at the foundation-soil interface, nonlinear coupling of soil and pore fluid, uplift or sliding of the foundation, nonlinear effects of gaps between the surrounding soil and the embedded structure and seismic isolation systems, none of which can be addressed explicitly at present. Appendix B of ASCE Standard 4 provides general guidance for NLSSI analysis but will not provide a methodology for performing the analysis. This paper provides a description of an NLSSI methodology developed for application to nuclear facilities, including NPPs. This methodology is described as series of sequential steps to produce reasonable results using any time-domain numerical code. These steps require some numerical capabilities, such as nonlinear soil constitutive models, which are also described in the paper.

Effect of domains configuration on crystal structure in ferroelectric ...

Indian Academy of Sciences (India)

2017-09-09

Sep 9, 2017 ... It is well known that domains and crystal structure control the physical properties of ferroelectrics. ... The as-prepared ceramics were crushed to fine pow- ders. ..... [1] Gao J, Xue D, Wang Y, Wang D, Zhang L, Wu H et al 2011.

Comparison of structure, function and regulation of plant cold shock domain proteins to bacterial and animal cold shock domain proteins.

Science.gov (United States)

Chaikam, Vijay; Karlson, Dale T

2010-01-01

The cold shock domain (CSD) is among the most ancient and well conserved nucleic acid binding domains from bacteria to higher animals and plants. The CSD facilitates binding to RNA, ssDNA and dsDNA and most functions attributed to cold shock domain proteins are mediated by this nucleic acid binding activity. In prokaryotes, cold shock domain proteins only contain a single CSD and are termed cold shock proteins (Csps). In animal model systems, various auxiliary domains are present in addition to the CSD and are commonly named Y-box proteins. Similar to animal CSPs, plant CSPs contain auxiliary C-terminal domains in addition to their N-terminal CSD. Cold shock domain proteins have been shown to play important roles in development and stress adaptation in wide variety of organisms. In this review, the structure, function and regulation of plant CSPs are compared and contrasted to the characteristics of bacterial and animal CSPs. [BMB reports 2010; 43(1): 1-8].

On two-point boundary correlations in the six-vertex model with domain wall boundary conditions

Science.gov (United States)

Colomo, F.; Pronko, A. G.

2005-05-01

The six-vertex model with domain wall boundary conditions on an N × N square lattice is considered. The two-point correlation function describing the probability of having two vertices in a given state at opposite (top and bottom) boundaries of the lattice is calculated. It is shown that this two-point boundary correlator is expressible in a very simple way in terms of the one-point boundary correlators of the model on N × N and (N - 1) × (N - 1) lattices. In alternating sign matrix (ASM) language this result implies that the doubly refined x-enumerations of ASMs are just appropriate combinations of the singly refined ones.

Structure and Dynamics of the tRNA-like Structure Domain of Brome Mosaic Virus

Science.gov (United States)

Vieweger, Mario; Nesbitt, David

2014-03-01

Conformational switching is widely accepted as regulatory mechanism in gene expression in bacterial systems. More recently, similar regulation mechanisms are emerging for viral systems. One of the most abundant and best studied systems is the tRNA-like structure domain that is found in a number of plant viruses across eight genera. In this work, the folding dynamics of the tRNA-like structure domain of Brome Mosaic Virus are investigated using single-molecule Fluorescence Resonance Energy Transfer techniques. In particular, Burst fluorescence is applied to observe metal-ion induced folding in freely diffusing RNA constructs resembling the 3'-terminal 169nt of BMV RNA3. Histograms of EFRET probabilities reveal a complex equilibrium of three distinct populations. A step-wise kinetic model for TLS folding is developed in accord with the evolution of conformational populations and structural information in the literature. In this mechanism, formation of functional TLS domains from unfolded RNAs requires two consecutive steps; 1) hybridization of a long-range stem interaction followed by 2) formation of a 3' pseudoknot. This three-state equilibrium is well described by step-wise dissociation constants K1(328(30) μM) and K2(1092(183) μM) for [Mg2+] and K1(74(6) mM) and K2(243(52) mM) for [Na+]-induced folding. The kinetic model is validated by oligo competition with the STEM interaction. Implications of this conformational folding mechanism are discussed in regards to regulation of virus replication.

A New Method for Determining Structure Ensemble: Application to a RNA Binding Di-Domain Protein.

Science.gov (United States)

Liu, Wei; Zhang, Jingfeng; Fan, Jing-Song; Tria, Giancarlo; Grüber, Gerhard; Yang, Daiwen

2016-05-10

Structure ensemble determination is the basis of understanding the structure-function relationship of a multidomain protein with weak domain-domain interactions. Paramagnetic relaxation enhancement has been proven a powerful tool in the study of structure ensembles, but there exist a number of challenges such as spin-label flexibility, domain dynamics, and overfitting. Here we propose a new (to our knowledge) method to describe structure ensembles using a minimal number of conformers. In this method, individual domains are considered rigid; the position of each spin-label conformer and the structure of each protein conformer are defined by three and six orthogonal parameters, respectively. First, the spin-label ensemble is determined by optimizing the positions and populations of spin-label conformers against intradomain paramagnetic relaxation enhancements with a genetic algorithm. Subsequently, the protein structure ensemble is optimized using a more efficient genetic algorithm-based approach and an overfitting indicator, both of which were established in this work. The method was validated using a reference ensemble with a set of conformers whose populations and structures are known. This method was also applied to study the structure ensemble of the tandem di-domain of a poly (U) binding protein. The determined ensemble was supported by small-angle x-ray scattering and nuclear magnetic resonance relaxation data. The ensemble obtained suggests an induced fit mechanism for recognition of target RNA by the protein. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Conserved intron positions in FGFR genes reflect the modular structure of FGFR and reveal stepwise addition of domains to an already complex ancestral FGFR.

Science.gov (United States)

Rebscher, Nicole; Deichmann, Christina; Sudhop, Stefanie; Fritzenwanker, Jens Holger; Green, Stephen; Hassel, Monika

2009-10-01

We have analyzed the evolution of fibroblast growth factor receptor (FGFR) tyrosine kinase genes throughout a wide range of animal phyla. No evidence for an FGFR gene was found in Porifera, but we tentatively identified an FGFR gene in the placozoan Trichoplax adhaerens. The gene encodes a protein with three immunoglobulin-like domains, a single-pass transmembrane, and a split tyrosine kinase domain. By superimposing intron positions of 20 FGFR genes from Placozoa, Cnidaria, Protostomia, and Deuterostomia over the respective protein domain structure, we identified ten ancestral introns and three conserved intron groups. Our analysis shows (1) that the position of ancestral introns correlates to the modular structure of FGFRs, (2) that the acidic domain very likely evolved in the last common ancestor of triploblasts, (3) that splicing of IgIII was enabled by a triploblast-specific insertion, and (4) that IgI is subject to substantial loss or duplication particularly in quickly evolving genomes. Moreover, intron positions in the catalytic domain of FGFRs map to the borders of protein subdomains highly conserved in other serine/threonine kinases. Nevertheless, these introns were introduced in metazoan receptor tyrosine kinases exclusively. Our data support the view that protein evolution dating back to the Cambrian explosion took place in such a short time window that only subtle changes in the domain structure are detectable in extant representatives of animal phyla. We propose that the first multidomain FGFR originated in the last common ancestor of Placozoa, Cnidaria, and Bilateria. Additional domains were introduced mainly in the ancestor of triploblasts and in the Ecdysozoa.

Structural Analysis of Covariance and Correlation Matrices.

Science.gov (United States)

Joreskog, Karl G.

1978-01-01

A general approach to analysis of covariance structures is considered, in which the variances and covariances or correlations of the observed variables are directly expressed in terms of the parameters of interest. The statistical problems of identification, estimation and testing of such covariance or correlation structures are discussed.…

Solution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP

Energy Technology Data Exchange (ETDEWEB)

Roldan, Jose L. Ortega [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain); Blackledge, Martin [Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, UJF UMR 5075, Protein Dynamics and Flexibility by NMR (France); Nuland, Nico A. J. van, E-mail: nvnuland@vub.ac.be [Vrije Universiteit Brussel, Structural Biology Brussels (Belgium); Azuaga, Ana I. [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain)

2011-06-15

CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney function. It contains three N-terminal SH3 domains that are able to interact among others with CD2, ALIX, c-Cbl and Ubiquitin. To understand the role of the individual SH3 domains of this adaptor protein we have performed a complete structural, thermodynamic and dynamic characterization of the separate domains using NMR and DSC. The energetic contributions to the stability and the backbone dynamics have been related to the structural features of each domain using the structure-based FoldX algorithm. We have found that the N-terminal SH3 domain of both adaptor proteins CD2AP and CIN85 are the most stable SH3 domains that have been studied until now. This high stability is driven by a more extensive network of intra-molecular interactions. We believe that this increased stabilization of N-terminal SH3 domains in adaptor proteins is crucial to maintain the necessary conformation to establish the proper interactions critical for the recruitment of their natural targets.

Crystal structure of a PFU-PUL domain pair of Saccharomyces cerevisiae Doa1/Ufd3.

Science.gov (United States)

Nishimasu, Rieko; Komori, Hirofumi; Higuchi, Yoshiki; Nishimasu, Hiroshi; Hiroaki, Hidekazu

2010-10-21

Doa1/Ufd3 is involved in ubiquitin (Ub)-dependent cellular processes in Saccharomyces cerevisiae, and consists of WD40, PFU, and PUL domains. Previous studies showed that the PFU and PUL domains interact with Ub and Hse1, and Cdc48, respectively. However, their detailed functional interactions with Doa1 remained elusive. We report the crystal structure of the PFU-PUL domain pair of yeast Doa1 at 1.9 Å resolution. The conserved surface of the PFU domain may be involved in binding to Ub and Hse1. Unexpectedly, the PUL domain consists of an Armadillo (ARM)-like repeat structure. The positively charged concave surface of the PUL domain may bind to the negatively charged C-terminal region of Cdc48. A structural comparison of Doa1 with Ufd2 revealed that they share a similar ARM-like repeat, supporting a model in which Doa1 and Ufd2 compete for Cdc48 binding and may dictate the fate of ubiquitinated proteins in the proteasome pathway.

Infrared scanning laser ophthalmoscope imaging of the macula and its correlation with functional loss and structural changes in patients with stargardt disease.

Science.gov (United States)

Anastasakis, Anastasios; Fishman, Gerald A; Lindeman, Martin; Genead, Mohamed A; Zhou, Wensheng

2011-05-01

To correlate the degree of functional loss with structural changes in patients with Stargardt disease. Eighteen eyes of 10 patients with Stargardt disease were studied. Scanning laser ophthalmoscope infrared images were compared with corresponding spectral-domain optical coherence tomography scans. Additionally, scanning laser ophthalmoscope microperimetry was performed, and results were superimposed on scanning laser ophthalmoscope infrared images and in selected cases on fundus autofluorescence images. Seventeen of 18 eyes showed a distinct hyporeflective foveal and/or perifoveal area with distinct borders on scanning laser ophthalmoscope infrared images, which was less evident on funduscopy and incompletely depicted in fundus autofluorescence images. This hyporeflective zone corresponded to areas of significantly elevated psychophysical thresholds on microperimetry testing, in addition to thinning of the retinal pigment epithelium and disorganization or loss of the photoreceptor cell inner segment-outer segment junction and external-limiting membrane on spectral-domain optical coherence tomography. Scanning laser ophthalmoscope infrared fundus images are useful for depicting retinal structural changes in patients with Stargardt disease. A spectral-domain optical coherence tomography/scanning laser ophthalmoscope microperimetry device allows for a direct correlation of structural abnormalities with functional defects that will likely be applicable for the determination of retinal areas for potential improvement of retinal function in these patients during future clinical trials and for the monitoring of the diseases' natural history.

Scattering analysis of periodic structures using finite-difference time-domain

CERN Document Server

ElMahgoub, Khaled; Elsherbeni, Atef Z

2012-01-01

Periodic structures are of great importance in electromagnetics due to their wide range of applications such as frequency selective surfaces (FSS), electromagnetic band gap (EBG) structures, periodic absorbers, meta-materials, and many others. The aim of this book is to develop efficient computational algorithms to analyze the scattering properties of various electromagnetic periodic structures using the finite-difference time-domain periodic boundary condition (FDTD/PBC) method. A new FDTD/PBC-based algorithm is introduced to analyze general skewed grid periodic structures while another algor

The Structural Basis for Activation and Inhibition of ZAP-70 Kinase Domain.

Science.gov (United States)

Huber, Roland G; Fan, Hao; Bond, Peter J

2015-10-01

ZAP-70 (Zeta-chain-associated protein kinase 70) is a tyrosine kinase that interacts directly with the activated T-cell receptor to transduce downstream signals, and is hence a major player in the regulation of the adaptive immune response. Dysfunction of ZAP-70 causes selective T cell deficiency that in turn results in persistent infections. ZAP-70 is activated by a variety of signals including phosphorylation of the kinase domain (KD), and binding of its regulatory tandem Src homology 2 (SH2) domains to the T cell receptor. The present study investigates molecular mechanisms of activation and inhibition of ZAP-70 via atomically detailed molecular dynamics simulation approaches. We report microsecond timescale simulations of five distinct states of the ZAP-70 KD, comprising apo, inhibited and three phosphorylated variants. Extensive analysis of local flexibility and correlated motions reveal crucial transitions between the states, thus elucidating crucial steps in the activation mechanism of the ZAP-70 KD. Furthermore, we rationalize previously observed staurosporine-bound crystal structures, suggesting that whilst the KD superficially resembles an "active-like" conformation, the inhibitor modulates the underlying protein dynamics and restricts it in a compact, rigid state inaccessible to ligands or cofactors. Finally, our analysis reveals a novel, potentially druggable pocket in close proximity to the activation loop of the kinase, and we subsequently use its structure in fragment-based virtual screening to develop a pharmacophore model. The pocket is distinct from classical type I or type II kinase pockets, and its discovery offers promise in future design of specific kinase inhibitors, whilst mutations in residues associated with this pocket are implicated in immunodeficiency in humans.

The Structural Basis for Activation and Inhibition of ZAP-70 Kinase Domain.

Directory of Open Access Journals (Sweden)

Roland G Huber

2015-10-01

Full Text Available ZAP-70 (Zeta-chain-associated protein kinase 70 is a tyrosine kinase that interacts directly with the activated T-cell receptor to transduce downstream signals, and is hence a major player in the regulation of the adaptive immune response. Dysfunction of ZAP-70 causes selective T cell deficiency that in turn results in persistent infections. ZAP-70 is activated by a variety of signals including phosphorylation of the kinase domain (KD, and binding of its regulatory tandem Src homology 2 (SH2 domains to the T cell receptor. The present study investigates molecular mechanisms of activation and inhibition of ZAP-70 via atomically detailed molecular dynamics simulation approaches. We report microsecond timescale simulations of five distinct states of the ZAP-70 KD, comprising apo, inhibited and three phosphorylated variants. Extensive analysis of local flexibility and correlated motions reveal crucial transitions between the states, thus elucidating crucial steps in the activation mechanism of the ZAP-70 KD. Furthermore, we rationalize previously observed staurosporine-bound crystal structures, suggesting that whilst the KD superficially resembles an "active-like" conformation, the inhibitor modulates the underlying protein dynamics and restricts it in a compact, rigid state inaccessible to ligands or cofactors. Finally, our analysis reveals a novel, potentially druggable pocket in close proximity to the activation loop of the kinase, and we subsequently use its structure in fragment-based virtual screening to develop a pharmacophore model. The pocket is distinct from classical type I or type II kinase pockets, and its discovery offers promise in future design of specific kinase inhibitors, whilst mutations in residues associated with this pocket are implicated in immunodeficiency in humans.

Dance and music share gray matter structural correlates.

Science.gov (United States)

Karpati, Falisha J; Giacosa, Chiara; Foster, Nicholas E V; Penhune, Virginia B; Hyde, Krista L

2017-02-15

Intensive practise of sensorimotor skills, such as music and dance, is associated with brain structural plasticity. While the neural correlates of music have been well-investigated, less is known about the neural correlates of dance. Additionally, the gray matter structural correlates of dance versus music training have not yet been directly compared. The objectives of the present study were to compare gray matter structure as measured by surface- and voxel-based morphometry between expert dancers, expert musicians and untrained controls, as well as to correlate gray matter structure with performance on dance- and music-related tasks. Dancers and musicians were found to have increased cortical thickness compared to controls in superior temporal regions. Gray matter structure in the superior temporal gyrus was also correlated with performance on dance imitation, rhythm synchronization and melody discrimination tasks. These results suggest that superior temporal regions are important in both dance- and music-related skills and may be affected similarly by both types of long-term intensive training. This work advances knowledge of the neural correlates of dance and music, as well as training-associated brain plasticity in general. Copyright © 2016 Elsevier B.V. All rights reserved.

Infrared imaging and spectral-domain optical coherence tomography findings correlate with microperimetry in acute macular neuroretinopathy: a case report

Directory of Open Access Journals (Sweden)

Grover Sandeep

2011-10-01

Full Text Available Abstract Introduction Spectral-domain optical coherence tomography findings in a patient with acute macular neuroretinopathy, and correlation with functional defects on microperimetry, are presented. Case presentation A 25-year old Caucasian woman presented with bitemporal field defects following an upper respiratory tract infection. Her visual acuity was 20/20 in both eyes and a dilated fundus examination revealed bilateral hyperpigmentary changes in the papillomacular bundle. Our patient underwent further evaluation with spectral-domain optical coherence tomography, infrared and fundus autofluorescence imaging. Functional changes were assessed by microperimetry. Infrared imaging showed the classic wedge-shaped defects and spectral-domain optical coherence tomography exhibited changes at the inner segment-outer segment junction, with a thickened outer plexiform layer overlying these areas. Fluorescein and indocyanine green angiography did not demonstrate any perfusion defects or any other abnormality. Microperimetry demonstrated focal elevation in threshold correlating with the wedge-shaped defects in both eyes. Conclusion Spectral-domain optical coherence tomography findings provide new evidence of the involvement of the outer plexiform layer of the retina in acute macular neuroretinopathy.

The retinal specific CD147 Ig0 domain: from molecular structure to biological activity

Science.gov (United States)

Redzic, Jasmina S.; Armstrong, Geoffrey S.; Isern, Nancy. G.; Jones, David N.M.; Kieft, Jeffrey S.; Eisenmesser, Elan Zohar

2011-01-01

CD147 is a type I transmembrane protein that is involved in inflammatory diseases, cancer progression, and multiple human pathogens utilize CD147 for efficient infection. In several cancers, CD147 expression is so high that it is now used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified, differing in their number of immunoglobulin (Ig)-like domains. These include CD147 Ig1-Ig2 that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 that is retinal specific and implicated in retinoblastoma. However, little is known in regard to the retinal specific CD147 Ig0 domain despite its potential role in retinoblastoma. We present the first crystal structure of the human CD147 Ig0 domain and show that the CD147 Ig0 domain is a crystallographic dimer with an I-type domain structure, which is maintained in solution. Furthermore, we have utilized our structural data together with mutagenesis to probe the biological activity of CD147-containing proteins both with and without the CD147 Ig0 domain within several model cell lines. Our findings reveal that the CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 domain has its own receptor distinct from that of the other CD147 Ig-like domains, CD147 Ig1-Ig2. Finally, we show that the CD147 Ig0 dimer is the functional unit required for activity and can be disrupted by a single point mutation. PMID:21620857

Fast identification of folded human protein domains expressed in E. coli suitable for structural analysis

Directory of Open Access Journals (Sweden)

Schlegel Brigitte

2004-03-01

Full Text Available Abstract Background High-throughput protein structure analysis of individual protein domains requires analysis of large numbers of expression clones to identify suitable constructs for structure determination. For this purpose, methods need to be implemented for fast and reliable screening of the expressed proteins as early as possible in the overall process from cloning to structure determination. Results 88 different E. coli expression constructs for 17 human protein domains were analysed using high-throughput cloning, purification and folding analysis to obtain candidates suitable for structural analysis. After 96 deep-well microplate expression and automated protein purification, protein domains were directly analysed using 1D 1H-NMR spectroscopy. In addition, analytical hydrophobic interaction chromatography (HIC was used to detect natively folded protein. With these two analytical methods, six constructs (representing two domains were quickly identified as being well folded and suitable for structural analysis. Conclusion The described approach facilitates high-throughput structural analysis. Clones expressing natively folded proteins suitable for NMR structure determination were quickly identified upon small scale expression screening using 1D 1H-NMR and/or analytical HIC. This procedure is especially effective as a fast and inexpensive screen for the 'low hanging fruits' in structural genomics.

Correlation of structure and function of the macula in patients with retinitis pigmentosa.

Science.gov (United States)

Battu, R; Khanna, A; Hegde, B; Berendschot, T T J M; Grover, S; Schouten, J S A G

2015-07-01

To correlate the structure of the macula, as measured by spectral-domain optical coherence tomography (SD-OCT) and function, as measured by microperimetry (MAIA) in patients with retinitis pigmentosa (RP) and relatively good visual acuity. Prospective, cross-sectional, non-intervention study. Patients with RP. Thirty patients with RP and good central visual acuity were identified. Each patient underwent SD-OCT of the macula and microperimetry. The images were overlaid using the custom-designed software. The retinal sensitivity by microperimetry was correlated with corresponding retinal thickness, as measured by the SD-OCT. ELM, COST, and IS/OS junction were scored as intact, disrupted, or absent. Comparing the retinal sensitivity on the MAIA with various measurements on the SD-OCT. The retinal sensitivity on the MAIA showed a significant correlation with total retinal thickness and outer retinal thickness on the SD-OCT. There was no association with either the inner retinal thickness or the choroidal thickness. ORT showed a statistically significant correlation with the anatomical classification of ELM (r=-0.76, Pmacula in patients with RP. These studies are important to establish surrogate markers that can be used as end points for various tests in future therapeutic clinical trials.

Crystallization behavior and domain structure in textured Pb(Zr0.52Ti0.48)O3 thin films by different annealing processes

International Nuclear Information System (INIS)

Huang, W.; Jiang, S.W.; Li, Y.R.; Zhu, J.; Zhang, Y.; Wei, X.H.; Zeng, H.Z.

2006-01-01

Amorphous Pb(Zr 0.52 Ti 0.48 )O 3 (PZT) thin films were prepared on the Pt/Ti/SiO 2 /Si substrates by radio-frequency magnetron sputtering at room temperature. After rapid thermal annealing (RTA) and conventional furnace annealing (CFA) at different temperatures, the films were transformed into polycrystalline PZT thin films with (111) and (100) orientation, respectively. The phase formation and ferroelectric domains correlated with different orientation were systematically investigated by X-ray diffraction and piezoresponse force microscopy. The results showed that the perovskite PZT crystal with [111] orientation hetero-nucleated preferentially on top of the PtPb intermetallic phase at the PZT/Pt interface during RTA process. It is of interest to find that the domain self-organized into a structure with rounded shape at the early stage of crystallization. While the nucleation of the films treated by CFA dominantly homo-nucleated, thus the (100) orientation grains with minimum surface energy were easy to grow. The texture effects on ferroelectric properties of PZT films were also discussed in relation to the domain structure

A new scaling approach for the mesoscale simulation of magnetic domain structures using Monte Carlo simulations

Energy Technology Data Exchange (ETDEWEB)

Radhakrishnan, B., E-mail: radhakrishnb@ornl.gov; Eisenbach, M.; Burress, T.A.

2017-06-15

Highlights: • Developed new scaling technique for dipole–dipole interaction energy. • Developed new scaling technique for exchange interaction energy. • Used scaling laws to extend atomistic simulations to micrometer length scale. • Demonstrated transition from mono-domain to vortex magnetic structure. • Simulated domain wall width and transition length scale agree with experiments. - Abstract: A new scaling approach has been proposed for the spin exchange and the dipole–dipole interaction energy as a function of the system size. The computed scaling laws are used in atomistic Monte Carlo simulations of magnetic moment evolution to predict the transition from single domain to a vortex structure as the system size increases. The width of a 180° – domain wall extracted from the simulated structures is in close agreement with experimentally values for an F–Si alloy. The transition size from a single domain to a vortex structure is also in close agreement with theoretically predicted and experimentally measured values for Fe.

Dynamics of Correlation Structure in Stock Market

Directory of Open Access Journals (Sweden)

Maman Abdurachman Djauhari

2014-01-01

Full Text Available In this paper a correction factor for Jennrich’s statistic is introduced in order to be able not only to test the stability of correlation structure, but also to identify the time windows where the instability occurs. If Jennrich’s statistic is only to test the stability of correlation structure along predetermined non-overlapping time windows, the corrected statistic provides us with the history of correlation structure dynamics from time window to time window. A graphical representation will be provided to visualize that history. This information is necessary to make further analysis about, for example, the change of topological properties of minimal spanning tree. An example using NYSE data will illustrate its advantages.

Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition.

Science.gov (United States)

Liu, Zhonghua; Wang, Chuanping; Rathkey, Joseph K; Yang, Jie; Dubyak, George R; Abbott, Derek W; Xiao, Tsan Sam

2018-05-01

Pyroptosis is an inflammatory form of programmed cell death that plays important roles in immune protection against infections and in inflammatory disorders. Gasdermin D (GSDMD) is an executor of pyroptosis upon cleavage by caspases-1/4/5/11 following canonical and noncanonical inflammasome activation. GSDMD N-terminal domain assembles membrane pores to induce cytolysis, whereas its C-terminal domain inhibits cell death through intramolecular association with the N domain. The molecular mechanisms of autoinhibition for GSDMD are poorly characterized. Here we report the crystal structures of the human and murine GSDMD C-terminal domains, which differ from those of the full-length murine GSDMA3 and the human GSDMB C-terminal domain. Mutations of GSDMD C-domain residues predicted to locate at its interface with the N-domain enhanced pyroptosis. Our results suggest that GSDMDs may employ a distinct mode of intramolecular domain interaction and autoinhibition, which may be relevant to its unique role in pyroptosis downstream of inflammasome activation. Copyright © 2018 Elsevier Ltd. All rights reserved.

The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger.

Science.gov (United States)

Alvadia, Carolina M; Sommer, Theis; Bjerregaard-Andersen, Kaare; Damkier, Helle Hasager; Montrasio, Michele; Aalkjaer, Christian; Morth, J Preben

2017-09-21

The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 Å resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family. A novel conserved Zn 2+ -binding motif present in the N-terminal domain of NDCBE is identified and characterized in vitro. Cellular studies confirm the Zn 2+ dependent transport of two electroneutral bicarbonate transporters, NCBE and NBCn1. The Zn 2+ site is mapped to a cluster of histidines close to the conserved ETARWLKFEE motif and likely plays a role in the regulation of this important motif. The combined structural and bioinformatics analysis provides a model that predicts with additional confidence the physiologically relevant interface between the cytoplasmic domain and the transmembrane domain.

Dimeric structure of the N-terminal domain of PriB protein from Thermoanaerobacter tengcongensis solved ab initio

Energy Technology Data Exchange (ETDEWEB)

Liebschner, Dorothee [National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); Brzezinski, Krzysztof [National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); University of Bialystok, 15-399 Bialystok (Poland); Dauter, Miroslawa [Argonne National Laboratory, Argonne, IL 60439 (United States); Dauter, Zbigniew, E-mail: dauter@anl.gov [National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); Nowak, Marta; Kur, Józef; Olszewski, Marcin, E-mail: dauter@anl.gov [Gdansk University of Technology, 80-952 Gdansk (Poland); National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States)

2012-12-01

The N-terminal domain of the PriB protein from the thermophilic bacterium T. tengcongensis (TtePriB) was expressed and its crystal structure has been solved at the atomic resolution of 1.09 Å by direct methods. PriB is one of the components of the bacterial primosome, which catalyzes the reactivation of stalled replication forks at sites of DNA damage. The N-terminal domain of the PriB protein from the thermophilic bacterium Thermoanaerobacter tengcongensis (TtePriB) was expressed and its crystal structure was solved at the atomic resolution of 1.09 Å by direct methods. The protein chain, which encompasses the first 104 residues of the full 220-residue protein, adopts the characteristic oligonucleotide/oligosaccharide-binding (OB) structure consisting of a five-stranded β-barrel filled with hydrophobic residues and equipped with four loops extending from the barrel. In the crystal two protomers dimerize, forming a six-stranded antiparallel β-sheet. The structure of the N-terminal OB domain of T. tengcongensis shows significant differences compared with mesophile PriBs. While in all other known structures of PriB a dimer is formed by two identical OB domains in separate chains, TtePriB contains two consecutive OB domains in one chain. However, sequence comparison of both the N-terminal and the C-terminal domains of TtePriB suggests that they have analogous structures and that the natural protein possesses a structure similar to a dimer of two N-terminal domains.

Controlling the anisotropy and domain structure with oblique deposition and substrate rotation

Directory of Open Access Journals (Sweden)

N. Chowdhury

2014-02-01

Full Text Available Effect of substrate rotation on anisotropy and domain structure for a thin ferromagnetic film has been investigated in this work. For this purpose Co films with 10 nm thickness have been prepared by sputtering with oblique angle of incidence for various substrate rotations. This method of preparation induces a uniaxial anisotropy due to shadow deposition effect. The magnetization reversal is studied by magneto-optic Kerr effect (MOKE based microscope in the longitudinal geometry. The Co films prepared by rotating the substrate with 10 and 20 rpm weakens the anisotropy but does not completely give isotropic films. But this leads to high dispersion in local grain anisotropy resulting in ripple and labyrinth domains. It is observed that the substrate rotation has moderate effect on uniaxial anisotropy but has significant effect on the magnetization reversal process and the domain structure.

FUNDUS AUTOFLUORESCENCE IN RUBELLA RETINOPATHY: Correlation With Photoreceptor Structure and Function.

Science.gov (United States)

Bukowska, Danuta M; Wan, Sue Ling; Chew, Avenell L; Chelva, Enid; Tang, Ivy; Mackey, David A; Chen, Fred K

2017-01-01

To illustrate altered fundus autofluorescence in rubella retinopathy and to investigate their relationships with photoreceptor structure and function using multimodal imaging. The authors report four cases of rubella retinopathy aged 8, 33, 42, and 50 years. All patients had dilated clinical fundus examination; wide-field color photography; blue, green, and near-infrared autofluorescence imaging and spectral domain optical coherence tomography. Two patients also underwent microperimetry and adaptive optics imaging. En face optical coherence tomography, cone mosaic, and microperimetry were coregistered with autofluorescence images. The authors explored the structure-function correlation. All four patients had a "salt-and-pepper" appearance on dilated fundus examination and wide-field color photography. There were variable-sized patches of hypoautofluorescence on both blue and near-infrared excitation in all four patients. Wave-guiding cones were visible and retinal sensitivity was intact over these regions. There was no correlation between hypoautofluorescence and regions of attenuated ellipsoid and interdigitation zones. Hyperautofluorescent lesions were also noted and some of these were pseudo-vitelliform lesions. Patchy hypoautofluorescence on near-infrared excitation can be a feature of rubella retinopathy. This may be due to abnormal melanin production or loss of melanin within retinal pigment epithelium cells harboring persistent rubella virus infection. Preservation of the ellipsoid zone, wave-guiding cones, and retinal sensitivity within hypoautofluorescent lesions suggest that these retinal pigment epithelium changes have only mild impact on photoreceptor cell function.

Comparison of S. cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site

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Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; Kenniston, Jon A.; Mendrola, Jeannine M.; Ferguson, Kathryn M.; Lemmon, Mark A.

2015-01-01

SUMMARY F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the S. cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences, and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip, and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity, and provide a basis for its prediction from sequence. PMID:25620000

Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

International Nuclear Information System (INIS)

Yun, Ji-Hye; Lee, Won Kyung; Kim, Heeyoun; Kim, Eunhee; Cheong, Chaejoon; Cho, Myeon Haeng; Lee, Weontae

2014-01-01

Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2 1–64 ) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2 1–64 and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences

Predicting detection performance with model observers: Fourier domain or spatial domain?

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Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-02-27

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution

International Nuclear Information System (INIS)

Chen, Liqing; Wang, Yujun; Wells, David; Toh, Diana; Harold, Hunt; Zhou, Jing; DiGiammarino, Enrico; Meehan, Edward J.

2006-01-01

The crystal structure of the SH3 domain of human osteoclast-stimulating factor has been determined and refined to the ultrahigh resolution of 1.07 Å. The structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors. Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and bone resorption. It is thought to act via an Src-related signaling pathway and contains SH3 and ankyrin-repeat domains which are involved in protein–protein interactions. As part of a structure-based anti-bone-loss drug-design program, the atomic resolution X-ray structure of the recombinant human OSF SH3 domain (hOSF-SH3) has been determined. The domain, residues 12–72, yielded crystals that diffracted to the ultrahigh resolution of 1.07 Å. The overall structure shows a characteristic SH3 fold consisting of two perpendicular β-sheets that form a β-barrel. Structure-based sequence alignment reveals that the putative proline-rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49, Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and Leu60, which might be key to designing specific inhibitors for hOSF to fight osteoporosis and related bone-loss diseases. There are a total of 13 well defined water molecules forming hydrogen bonds with the above residues in and around the peptide-binding pocket. Some of those water molecules might be important for drug-design approaches. The hOSF-SH3 structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors

alpha-helical structural elements within the voltage-sensing domains of a K(+) channel.

Science.gov (United States)

Li-Smerin, Y; Hackos, D H; Swartz, K J

2000-01-01

Voltage-gated K(+) channels are tetramers with each subunit containing six (S1-S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5-S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1-S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K(+) channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of alpha-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting alpha-helical secondary structure. In addition, both the S1-S2 and S3-S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain.

Hum-mPLoc 3.0: prediction enhancement of human protein subcellular localization through modeling the hidden correlations of gene ontology and functional domain features.

Science.gov (United States)

Zhou, Hang; Yang, Yang; Shen, Hong-Bin

2017-03-15

Protein subcellular localization prediction has been an important research topic in computational biology over the last decade. Various automatic methods have been proposed to predict locations for large scale protein datasets, where statistical machine learning algorithms are widely used for model construction. A key step in these predictors is encoding the amino acid sequences into feature vectors. Many studies have shown that features extracted from biological domains, such as gene ontology and functional domains, can be very useful for improving the prediction accuracy. However, domain knowledge usually results in redundant features and high-dimensional feature spaces, which may degenerate the performance of machine learning models. In this paper, we propose a new amino acid sequence-based human protein subcellular location prediction approach Hum-mPLoc 3.0, which covers 12 human subcellular localizations. The sequences are represented by multi-view complementary features, i.e. context vocabulary annotation-based gene ontology (GO) terms, peptide-based functional domains, and residue-based statistical features. To systematically reflect the structural hierarchy of the domain knowledge bases, we propose a novel feature representation protocol denoted as HCM (Hidden Correlation Modeling), which will create more compact and discriminative feature vectors by modeling the hidden correlations between annotation terms. Experimental results on four benchmark datasets show that HCM improves prediction accuracy by 5-11% and F 1 by 8-19% compared with conventional GO-based methods. A large-scale application of Hum-mPLoc 3.0 on the whole human proteome reveals proteins co-localization preferences in the cell. www.csbio.sjtu.edu.cn/bioinf/Hum-mPLoc3/. hbshen@sjtu.edu.cn. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Comparative structure-function characterization of the saposin-like domains from potato, barley, cardoon and Arabidopsis aspartic proteases.

Science.gov (United States)

Bryksa, Brian C; Grahame, Douglas A; Yada, Rickey Y

2017-05-01

The present study characterized the aspartic protease saposin-like domains of four plant species, Solanum tuberosum (potato), Hordeum vulgare L. (barley), Cynara cardunculus L. (cardoon; artichoke thistle) and Arabidopsis thaliana, in terms of bilayer disruption and fusion, and structure pH-dependence. Comparison of the recombinant saposin-like domains revealed that each induced leakage of bilayer vesicles composed of a simple phospholipid mixture with relative rates Arabidopsis>barley>cardoon>potato. When compared for leakage of bilayer composed of a vacuole-like phospholipid mixture, leakage was approximately five times higher for potato saposin-like domain compared to the others. In terms of fusogenic activity, distinctions between particle size profiles were noted among the four proteins, particularly for potato saposin-like domain. Bilayer fusion assays in reducing conditions resulted in altered fusion profiles except in the case of cardoon saposin-like domain which was virtually unchanged. Secondary structure profiles were similar across all four proteins under different pH conditions, although cardoon saposin-like domain appeared to have higher overall helix structure. Furthermore, increases in Trp emission upon protein-bilayer interactions suggested that protein structure rearrangements equilibrated with half-times ranging from 52 to 120s, with cardoon saposin-like domain significantly slower than the other three species. Overall, the present findings serve as a foundation for future studies seeking to delineate protein structural features and motifs in protein-bilayer interactions based upon variability in plant aspartic protease saposin-like domain structures. Copyright © 2017 Elsevier B.V. All rights reserved.

Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

Science.gov (United States)

Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

Structure of DSM-5 and ICD-11 personality domains in Iranian community sample.

Science.gov (United States)

Lotfi, Mozhgan; Bach, Bo; Amini, Mahdi; Simonsen, Erik

2018-02-02

Personality disorders (PD) have been deemed the most problematic diagnostic grouping in terms of validity and utility, which particularly applies to non-Western societies. The current study evaluated the structural validity of PD trait domains in the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) Section III and the proposed International Classification of Diseases-11 (ICD-11) in the Iranian population. Community-dwelling adults (n = 285; 66% women) were administered the Personality Inventory for DSM-5, whereas the proposed ICD-11 trait domains were delineated using an algorithm for Personality Inventory for DSM-5 trait facets. The five-factor organization and higher-order hierarchical structure of both models were examined using exploratory structural equation modelling analyses. The five-factor exploratory structural equation modelling loadings overall resembled international findings on DSM-5 Section III traits (including Psychoticism), whereas the ICD-11 five-factor structure aligned with the proposed ICD-11 domain features (including Anankastia). Additionally, we identified a hierarchical structure from one to five factors for both models that conceptually aligned with established models of personality and psychopathology. This study provided initial support for the structural validity of DSM-5 and ICD-11 PD trait models in Iranian culture. Future research warrants replication in larger samples and clinical populations. Copyright © 2018 John Wiley & Sons, Ltd. Copyright © 2018 John Wiley & Sons, Ltd.

Nanoscopic studies of domain structure dynamics in ferroelectric La:HfO2 capacitors

Science.gov (United States)

Buragohain, P.; Richter, C.; Schenk, T.; Lu, H.; Mikolajick, T.; Schroeder, U.; Gruverman, A.

2018-05-01

Visualization of domain structure evolution under an electrical bias has been carried out in ferroelectric La:HfO2 capacitors by a combination of Piezoresponse Force Microscopy (PFM) and pulse switching techniques to study the nanoscopic mechanism of polarization reversal and the wake-up process. It has been directly shown that the main mechanism behind the transformation of the polarization hysteretic behavior and an increase in the remanent polarization value upon the alternating current cycling is electrically induced domain de-pinning. PFM imaging and local spectroscopy revealed asymmetric switching in the La:HfO2 capacitors due to a significant imprint likely caused by the different boundary conditions at the top and bottom interfaces. Domain switching kinetics can be well-described by the nucleation limited switching model characterized by a broad distribution of the local switching times. It has been found that the domain velocity varies significantly throughout the switching process indicating strong interaction with structural defects.

Structural matching of ferroelectric domains and associated distortion in potassium titanyl phosphate crystals

CERN Document Server

Pernot-Rejmankova, P; Cloetens, P; Lyford, T; Baruchel, J

2003-01-01

The surface deformation and atomic-level distortions associated with crystal structural matching at ferroelectric inversion domain walls are investigated in periodically poled potassium titanyl phosphate (KTP) crystals. A deformation, of the order of 10 sup - sup 8 m in scale and having the periodicity of the domains, is observed at the surfaces by optical interferometry. It is discussed in terms of the piezoelectric effect. The matching of the crystal structures at the domain walls is studied by combining the hard x-ray Fresnel phase-imaging technique with Bragg diffraction imaging methods ('Bragg-Fresnel imaging') and using synchrotron radiation. Quantitative analysis of the contrast of the Bragg-Fresnel images recorded as a function of the propagation distance is demonstrated to allow the determination of how the domains are matched at the atomic (unit cell) level, even though the spatial resolution of the images is on the scale of micrometres. The atom P(1) is determined as the linking atom for connecting...

Correlation between Crystallographic and Magnetic Domains at Co/NiO(001) Interfaces

Energy Technology Data Exchange (ETDEWEB)

Ohldag, H.; van der Laan, G.; Arenholz, E.

2008-12-18

Using soft x-ray spectromicroscopy we show that NiO(001) exhibits a crystallographic and magnetic domain structure near the surface identical to that of the bulk. Upon Co deposition a perpendicular coupling between the Ni and Co moments is observed that persists even after formation of uncompensated Ni spins at the interface through annealing. The chemical composition at the interface alters its crystallographic structure and leads to a reorientation of the Ni moments from the <112> to the <110> direction. We show that this reorientation is driven by changes in the magnetocrystalline anisotropy rather than exchange coupling mediated by residual uncompensated spins.

Tip-induced domain structures and polarization switching in ferroelectric amino acid glycine

Energy Technology Data Exchange (ETDEWEB)

Seyedhosseini, E., E-mail: Seyedhosseini@ua.pt; Ivanov, M. [CICECO-Aveiro Institute of Materials and Department of Physics, University of Aveiro, 3810-193 Aveiro (Portugal); Bdikin, I. [TEMA and Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Vasileva, D. [Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg (Russian Federation); Kudryavtsev, A. [Moscow State Institute of Radioengineering, Electronics and Automation, 119454 Moscow (Russian Federation); Rodriguez, B. J. [Conway Institute of Biomolecular and Biomedical Research and School of Physics, University College Dublin, Dublin (Ireland); Kholkin, A. L. [CICECO-Aveiro Institute of Materials and Department of Physics, University of Aveiro, 3810-193 Aveiro (Portugal); Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg (Russian Federation)

2015-08-21

Bioorganic ferroelectrics and piezoelectrics are becoming increasingly important in view of their intrinsic compatibility with biological environment and biofunctionality combined with strong piezoelectric effect and a switchable polarization at room temperature. Here, we study tip-induced domain structures and polarization switching in the smallest amino acid β-glycine, representing a broad class of non-centrosymmetric amino acids. We show that β-glycine is indeed a room-temperature ferroelectric and polarization can be switched by applying a bias to non-polar cuts via a conducting tip of atomic force microscope (AFM). Dynamics of these in-plane domains is studied as a function of an applied voltage and pulse duration. The domain shape is dictated by polarization screening at the domain boundaries and mediated by growth defects. Thermodynamic theory is applied to explain the domain propagation induced by the AFM tip. Our findings suggest that the properties of β-glycine are controlled by the charged domain walls which in turn can be manipulated by an external bias.

Ferromagnetic domain structures and spin configurations measured in doped manganite

DEFF Research Database (Denmark)

He, J.Q.; Volkov, V.V.; Beleggia, Marco

2010-01-01

We report on measurements of the spin configuration across ferromagnetic domains in La0.325Pr0.3Ca0.375MnO3 films obtained by means of low-temperature Lorentz electron microscopy with in situ magnetizing capabilities. Due to the particular crystal symmetry of the material, we observe two sets of ...... and the crystal symmetry might affect the magnetoresistivity under an applied magnetic field in a strongly correlated electron system....

Crystal Structure of the Extracellular Cholinesterase-Like Domain from Neuroligin-2

Energy Technology Data Exchange (ETDEWEB)

Koehnke,J.; Jin, X.; Budreck, E.; Posy, S.; Scheiffele, P.; Hnoig, B.; Shapiro, L.

2008-01-01

Neuroligins (NLs) are catalytically inactive members of a family of cholinesterase-like transmembrane proteins that mediate cell adhesion at neuronal synapses. Postsynaptic neuroligins engage in Ca2+-dependent transsynaptic interactions via their extracellular cholinesterase domain with presynaptic neurexins (NRXs). These interactions may be regulated by two short splice insertions (termed A and B) in the NL cholinesterase domain. Here, we present the 3.3- Angstroms crystal structure of the ectodomain from NL2 containing splice insertion A (NL2A). The overall structure of NL2A resembles that of cholinesterases, but several structural features are unique to the NL proteins. First, structural elements surrounding the esterase active-site region differ significantly between active esterases and NL2A. On the opposite surface of the NL2A molecule, the positions of the A and B splice insertions identify a candidate NRX interaction site of the NL protein. Finally, sequence comparisons of NL isoforms allow for mapping the location of residues of previously identified mutations in NL3 and NL4 found in patients with autism spectrum disorders. Overall, the NL2 structure promises to provide a valuable model for dissecting NL isoform- and synapse-specific functions.

Structured Literature Review of disruptive innovation theory within the digital domain

DEFF Research Database (Denmark)

Vesti, Helle; Nielsen, Christian; Rosenstand, Claus Andreas Foss

2017-01-01

The area of interest is disruption is the digital domain. The research questions are: How has the disruption and digital disruption literature developed over time? What is the research focus into disruption regarding the digital domain and how has this changed over time? Which methods are being...... utilized in research regarding disruption and digital disruption? Where are the key contributors to disruption in general and in digital disruption? Is there a future for digital disruption research? The method is a Structured Literature Review (SLR). The contribution is the results of an analysis of 95...... publications within the field of disruption in the digital domain and disruptive innovation theory in general. Works of twelve practitioners and 83 academics are investigated....

The structure of a conserved Piezo channel domain reveals a novel beta sandwich fold

Science.gov (United States)

Kamajaya, Aron; Kaiser, Jens; Lee, Jonas; Reid, Michelle; Rees, Douglas C.

2014-01-01

Summary Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a novel beta sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in Dehydrated Hereditary Stomatocytosis (DHS) patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. PMID:25242456

Solution structure of tensin2 SH2 domain and its phosphotyrosine-independent interaction with DLC-1.

Directory of Open Access Journals (Sweden)

Kun Dai

Full Text Available Src homology 2 (SH2 domain is a conserved module involved in various biological processes. Tensin family member was reported to be involved in tumor suppression by interacting with DLC-1 (deleted-in-liver-cancer-1 via its SH2 domain. We explore here the important questions that what the structure of tensin2 SH2 domain is, and how it binds to DLC-1, which might reveal a novel binding mode.Tensin2 SH2 domain adopts a conserved SH2 fold that mainly consists of five β-strands flanked by two α-helices. Most SH2 domains recognize phosphorylated ligands specifically. However, tensin2 SH2 domain was identified to interact with nonphosphorylated ligand (DLC-1 as well as phosphorylated ligand.We determined the solution structure of tensin2 SH2 domain using NMR spectroscopy, and revealed the interactions between tensin2 SH2 domain and its ligands in a phosphotyrosine-independent manner.

Polar and chemical domain structures of lead scandium tantalate (PST)

International Nuclear Information System (INIS)

Peng, J.L.; Bursill, L.A.

1993-01-01

The local structure of chemical and polar domains and domain walls is determined directly by atomic resolution high-resolution electron microscopy. Thus the Pb, Ta and Sc atomic positions may be located in the images of very thin crystals. Furthermore the Pb cation displacements away from the ideal perovskite A-site have been measured directly for the first time. Local variations in polarization direction may be mapped directly off the images, provided certain electron optical conditions are met. The results are relevant to recent theories of polar-glass behaviour in relaxor-type complex oxide functional ceramics. 17 refs., 9 figs

Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

International Nuclear Information System (INIS)

Vognsen, Tina; Kristensen, Ole

2012-01-01

Highlights: ► The crystal structure of the NTF2-like domain of Rasputin protein is presented. ► Differences to known ligand binding sites of nuclear transport factor 2 are discussed. ► A new ligand binding site for the Rasputin and G3BP proteins is proposed. -- Abstract: The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a β-sheet and three α-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.

Mutations in actin used for structural studies partially disrupt β-thymosin/WH2 domains interaction.

Science.gov (United States)

Deville, Célia; Girard-Blanc, Christine; Assrir, Nadine; Nhiri, Naïma; Jacquet, Eric; Bontems, François; Renault, Louis; Petres, Stéphane; van Heijenoort, Carine

2016-10-01

Understanding the structural basis of actin cytoskeleton remodeling requires stabilization of actin monomers, oligomers, and filaments in complex with partner proteins, using various biochemical strategies. Here, we report a dramatic destabilization of the dynamic interaction with a model β-thymosin/WH2 domain induced by mutations in actin. This result underlines that mutant actins should be used with prudence to characterize interactions with intrinsically disordered partners as destabilization of dynamic interactions, although identifiable by NMR, may be invisible to other structural techniques. It also highlights how both β-thymosin/WH2 domains and actin tune local structure and dynamics in regulatory processes involving intrinsically disordered domains. © 2016 Federation of European Biochemical Societies.

Structure of the C-terminal domain of nsp4 from feline coronavirus

International Nuclear Information System (INIS)

Manolaridis, Ioannis; Wojdyla, Justyna A.; Panjikar, Santosh; Snijder, Eric J.; Gorbalenya, Alexander E.; Berglind, Hanna; Nordlund, Pär; Coutard, Bruno; Tucker, Paul A.

2009-01-01

The structure of the cytosolic C-terminal domain of nonstructural protein 4 from feline coronavirus has been determined and analyzed. Coronaviruses are a family of positive-stranded RNA viruses that includes important pathogens of humans and other animals. The large coronavirus genome (26–31 kb) encodes 15–16 nonstructural proteins (nsps) that are derived from two replicase polyproteins by autoproteolytic processing. The nsps assemble into the viral replication–transcription complex and nsp3, nsp4 and nsp6 are believed to anchor this enzyme complex to modified intracellular membranes. The largest part of the coronavirus nsp4 subunit is hydrophobic and is predicted to be embedded in the membranes. In this report, a conserved C-terminal domain (∼100 amino-acid residues) has been delineated that is predicted to face the cytoplasm and has been isolated as a soluble domain using library-based construct screening. A prototypical crystal structure at 2.8 Å resolution was obtained using nsp4 from feline coronavirus. Unmodified and SeMet-substituted proteins were crystallized under similar conditions, resulting in tetragonal crystals that belonged to space group P4 3 . The phase problem was initially solved by single isomorphous replacement with anomalous scattering (SIRAS), followed by molecular replacement using a SIRAS-derived composite model. The structure consists of a single domain with a predominantly α-helical content displaying a unique fold that could be engaged in protein–protein interactions

Structure of the C-terminal domain of nsp4 from feline coronavirus

Energy Technology Data Exchange (ETDEWEB)

Manolaridis, Ioannis; Wojdyla, Justyna A.; Panjikar, Santosh [EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg (Germany); Snijder, Eric J.; Gorbalenya, Alexander E. [Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden (Netherlands); Berglind, Hanna; Nordlund, Pär [Division of Biophysics, Department of Medical Biochemistry and Biophysics, Scheeles väg 2, Karolinska Institute, SE-171 77 Stockholm (Sweden); Coutard, Bruno [Laboratoire Architecture et Fonction des Macromolécules Biologiques, UMR 6098, AFMB-CNRS-ESIL, Case 925, 163 Avenue de Luminy, 13288 Marseille (France); Tucker, Paul A., E-mail: tucker@embl-hamburg.de [EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg (Germany)

2009-08-01

The structure of the cytosolic C-terminal domain of nonstructural protein 4 from feline coronavirus has been determined and analyzed. Coronaviruses are a family of positive-stranded RNA viruses that includes important pathogens of humans and other animals. The large coronavirus genome (26–31 kb) encodes 15–16 nonstructural proteins (nsps) that are derived from two replicase polyproteins by autoproteolytic processing. The nsps assemble into the viral replication–transcription complex and nsp3, nsp4 and nsp6 are believed to anchor this enzyme complex to modified intracellular membranes. The largest part of the coronavirus nsp4 subunit is hydrophobic and is predicted to be embedded in the membranes. In this report, a conserved C-terminal domain (∼100 amino-acid residues) has been delineated that is predicted to face the cytoplasm and has been isolated as a soluble domain using library-based construct screening. A prototypical crystal structure at 2.8 Å resolution was obtained using nsp4 from feline coronavirus. Unmodified and SeMet-substituted proteins were crystallized under similar conditions, resulting in tetragonal crystals that belonged to space group P4{sub 3}. The phase problem was initially solved by single isomorphous replacement with anomalous scattering (SIRAS), followed by molecular replacement using a SIRAS-derived composite model. The structure consists of a single domain with a predominantly α-helical content displaying a unique fold that could be engaged in protein–protein interactions.

Structural Time Domain Identification (STDI) Toolbox for Use with MATLAB

DEFF Research Database (Denmark)

Kirkegaard, Poul Henning; Andersen, P.; Brincker, Rune

1997-01-01

The Structural Time Domain Identification (STDI) toolbox for use with MATLABTM is developed at Aalborg University, Denmark, based on the system identification research performed during recent years. By now, a reliable set of functions offers a wide spectrum of services for all the important steps...

Structural Time Domain Identification (STDI) Toolbox for Use with MATLAB

DEFF Research Database (Denmark)

Kirkegaard, Poul Henning; Andersen, P.; Brincker, Rune

The Structural Time Domain Identification (STDI) toolbox for use with MATLABTM is developed at Aalborg University, Denmark, based on the system identification research performed during recent years. By now, a reliable set of functions offers a wide spectrum of services for all the important steps...

Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.

Science.gov (United States)

Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi

2013-12-01

AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

Novel Chiral Magnetic Domain Wall Structure in Fe/Ni/Cu(001) Films

Science.gov (United States)

Chen, G.; Zhu, J.; Quesada, A.; Li, J.; N'Diaye, A. T.; Huo, Y.; Ma, T. P.; Chen, Y.; Kwon, H. Y.; Won, C.; Qiu, Z. Q.; Schmid, A. K.; Wu, Y. Z.

2013-04-01

Using spin-polarized low energy electron microscopy, we discovered a new type of domain wall structure in perpendicularly magnetized Fe/Ni bilayers grown epitaxially on Cu(100). Specifically, we observed unexpected Néel-type walls with fixed chirality in the magnetic stripe phase. Furthermore, we find that the chirality of the domain walls is determined by the film growth order with the chirality being right handed in Fe/Ni bilayers and left handed in Ni/Fe bilayers, suggesting that the underlying mechanism is the Dzyaloshinskii-Moriya interaction at the film interfaces. Our observations may open a new route to control chiral spin structures using interfacial engineering in transition metal heterostructures.

α-Helical Structural Elements within the Voltage-Sensing Domains of a K+ Channel

Science.gov (United States)

Li-Smerin, Yingying; Hackos, David H.; Swartz, Kenton J.

2000-01-01

Voltage-gated K+ channels are tetramers with each subunit containing six (S1–S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5–S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1–S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K+ channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of α-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting α-helical secondary structure. In addition, both the S1–S2 and S3–S4 linkers exhibited substantial helical character. The distribution of gating perturbations for S1 and S2 suggest that these two helices interact primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain. PMID:10613917

Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor

Energy Technology Data Exchange (ETDEWEB)

Peng, Guiqing; Sun, Dawei; Rajashankar, Kanagalaghatta R.; Qian, Zhaohui; Holmes, Kathryn V.; Li, Fang (Cornell); (UMM-MED); (Colorado)

2011-09-28

Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same {beta}-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusive protein-protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the {beta}-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.

Dynamic Analysis of Partially Embedded Structures Considering Soil-Structure Interaction in Time Domain

Directory of Open Access Journals (Sweden)

Sanaz Mahmoudpour

2011-01-01

Full Text Available Analysis and design of structures subjected to arbitrary dynamic loadings especially earthquakes have been studied during past decades. In practice, the effects of soil-structure interaction on the dynamic response of structures are usually neglected. In this study, the effect of soil-structure interaction on the dynamic response of structures has been examined. The substructure method using dynamic stiffness of soil is used to analyze soil-structure system. A coupled model based on finite element method and scaled boundary finite element method is applied. Finite element method is used to analyze the structure, and scaled boundary finite element method is applied in the analysis of unbounded soil region. Due to analytical solution in the radial direction, the radiation condition is satisfied exactly. The material behavior of soil and structure is assumed to be linear. The soil region is considered as a homogeneous half-space. The analysis is performed in time domain. A computer program is prepared to analyze the soil-structure system. Comparing the results with those in literature shows the exactness and competency of the proposed method.

Structure of the N-terminal domain of the protein Expansion: an ‘Expansion’ to the Smad MH2 fold

International Nuclear Information System (INIS)

Beich-Frandsen, Mads; Aragón, Eric; Llimargas, Marta; Benach, Jordi; Riera, Antoni; Pous, Joan; Macias, Maria J.

2015-01-01

Expansion is a modular protein that is conserved in protostomes. The first structure of the N-terminal domain of Expansion has been determined at 1.6 Å resolution and the new Nα-MH2 domain was found to belong to the Smad/FHA superfamily of structures. Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily

Structure of the N-terminal domain of the protein Expansion: an ‘Expansion’ to the Smad MH2 fold

Energy Technology Data Exchange (ETDEWEB)

Beich-Frandsen, Mads; Aragón, Eric [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Llimargas, Marta [Institut de Biologia Molecular de Barcelona, IBMB–CSIC, Baldiri Reixac 10, 08028 Barcelona (Spain); Benach, Jordi [ALBA Synchrotron, BP 1413, km 3.3, Cerdanyola del Vallès (Spain); Riera, Antoni [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Universitat de Barcelona, Martí i Franqués 1-11, 08028 Barcelona (Spain); Pous, Joan [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Platform of Crystallography IBMB–CSIC, Baldiri Reixac 10, 08028 Barcelona (Spain); Macias, Maria J., E-mail: maria.macias@irbbarcelona.org [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010 Barcelona (Spain)

2015-04-01

Expansion is a modular protein that is conserved in protostomes. The first structure of the N-terminal domain of Expansion has been determined at 1.6 Å resolution and the new Nα-MH2 domain was found to belong to the Smad/FHA superfamily of structures. Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily.

Structural analysis of poly-SUMO chain recognition by the RNF4-SIMs domain.

Science.gov (United States)

Kung, Camy C-H; Naik, Mandar T; Wang, Szu-Huan; Shih, Hsiu-Ming; Chang, Che-Chang; Lin, Li-Ying; Chen, Chia-Lin; Ma, Che; Chang, Chi-Fon; Huang, Tai-Huang

2014-08-15

The E3 ubiquitin ligase RNF4 (RING finger protein 4) contains four tandem SIM [SUMO (small ubiquitin-like modifier)-interaction motif] repeats for selective interaction with poly-SUMO-modified proteins, which it targets for degradation. We employed a multi-faceted approach to characterize the structure of the RNF4-SIMs domain and the tetra-SUMO2 chain to elucidate the interaction between them. In solution, the SIM domain was intrinsically disordered and the linkers of the tetra-SUMO2 were highly flexible. Individual SIMs of the RNF4-SIMs domains bind to SUMO2 in the groove between the β2-strand and the α1-helix parallel to the β2-strand. SIM2 and SIM3 bound to SUMO with a high affinity and together constituted the recognition module necessary for SUMO binding. SIM4 alone bound to SUMO with low affinity; however, its contribution to tetra-SUMO2 binding avidity is comparable with that of SIM3 when in the RNF4-SIMs domain. The SAXS data of the tetra-SUMO2-RNF4-SIMs domain complex indicate that it exists as an ordered structure. The HADDOCK model showed that the tandem RNF4-SIMs domain bound antiparallel to the tetra-SUMO2 chain orientation and wrapped around the SUMO protamers in a superhelical turn without imposing steric hindrance on either molecule.

Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.

Directory of Open Access Journals (Sweden)

Neil J Ball

2016-11-01

Full Text Available The Spumaretrovirinae, or foamy viruses (FVs are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV. The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA and C-terminal domains (CtDCA of archetypal orthoretroviral capsid protein (CA. Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN-CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold.

Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid

Science.gov (United States)

Dutta, Moumita; Pollard, Dominic J.; Goldstone, David C.; Ramos, Andres; Müllers, Erik; Stirnnagel, Kristin; Stanke, Nicole; Lindemann, Dirk; Taylor, William R.; Rosenthal, Peter B.

2016-01-01

The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN—CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold. PMID:27829070

Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions

Science.gov (United States)

Bunney, Tom D.; Cole, Ambrose R.; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W.; Katan, Matilda

2014-01-01

Summary Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition. PMID:25435325

A crystal structure of the Dengue virus NS5 protein reveals a novel inter-domain interface essential for protein flexibility and virus replication.

Directory of Open Access Journals (Sweden)

Yongqian Zhao

2015-03-01

Full Text Available Flavivirus RNA replication occurs within a replication complex (RC that assembles on ER membranes and comprises both non-structural (NS viral proteins and host cofactors. As the largest protein component within the flavivirus RC, NS5 plays key enzymatic roles through its N-terminal methyltransferase (MTase and C-terminal RNA-dependent-RNA polymerase (RdRp domains, and constitutes a major target for antivirals. We determined a crystal structure of the full-length NS5 protein from Dengue virus serotype 3 (DENV3 at a resolution of 2.3 Å in the presence of bound SAH and GTP. Although the overall molecular shape of NS5 from DENV3 resembles that of NS5 from Japanese Encephalitis Virus (JEV, the relative orientation between the MTase and RdRp domains differs between the two structures, providing direct evidence for the existence of a set of discrete stable molecular conformations that may be required for its function. While the inter-domain region is mostly disordered in NS5 from JEV, the NS5 structure from DENV3 reveals a well-ordered linker region comprising a short 310 helix that may act as a swivel. Solution Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS analysis reveals an increased mobility of the thumb subdomain of RdRp in the context of the full length NS5 protein which correlates well with the analysis of the crystallographic temperature factors. Site-directed mutagenesis targeting the mostly polar interface between the MTase and RdRp domains identified several evolutionarily conserved residues that are important for viral replication, suggesting that inter-domain cross-talk in NS5 regulates virus replication. Collectively, a picture for the molecular origin of NS5 flexibility is emerging with profound implications for flavivirus replication and for the development of therapeutics targeting NS5.

Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Yun, Ji-Hye [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Won Kyung [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Eunhee; Cheong, Chaejoon [Magnetic Resonance Team, Korea Basic Science Institute (KBSI), Ochang, Chungbuk 363-883 (Korea, Republic of); Cho, Myeon Haeng [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2014-09-26

Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2{sub 1–64}) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2{sub 1–64} and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences.

Structural analyses of the Ankyrin Repeat Domain of TRPV6 and related TRPV ion channels†‡

OpenAIRE

Phelps, Christopher B.; Huang, Robert J.; Lishko, Polina V.; Wang, Ruiqi R.; Gaudet, Rachelle

2008-01-01

Transient Receptor Potential (TRP) proteins are cation channels composed of a transmembrane domain flanked by large N- and C-terminal cytoplasmic domains. All members of the vanilloid family of TRP channels (TRPV) possess an N-terminal ankyrin repeat domain (ARD). The ARD of mammalian TRPV6, an important regulator of calcium uptake and homeostasis, is essential for channel assembly and regulation. The 1.7 Å crystal structure of the TRPV6-ARD reveals conserved structural elements unique to the...

Residual strain sensor using Al-packaged optical fiber and Brillouin optical correlation domain analysis.

Science.gov (United States)

Choi, Bo-Hun; Kwon, Il-Bum

2015-03-09

We propose a distributed residual strain sensor that uses an Al-packaged optical fiber for the first time. The residual strain which causes Brillouin frequency shifts in the optical fiber was measured using Brillouin optical correlation domain analysis with 2 cm spatial resolution. We quantified the Brillouin frequency shifts in the Al-packaged optical fiber by the tensile stress and compared them for a varying number of Al layers in the optical fiber. The Brillouin frequency shift of an optical fiber with one Al layer had a slope of 0.038 MHz/με with respect to tensile stress, which corresponds to 78% of that for an optical fiber without Al layers. After removal of the stress, 87% of the strain remained as residual strain. When different tensile stresses were randomly applied, the strain caused by the highest stress was the only one detected as residual strain. The residual strain was repeatedly measured for a time span of nine months for the purpose of reliability testing, and there was no change in the strain except for a 4% reduction, which is within the error tolerance of the experiment. A composite material plate equipped with our proposed Al-packaged optical fiber sensor was hammered for impact experiment and the residual strain in the plate was successfully detected. We suggest that the Al-packaged optical fiber can be adapted as a distributed strain sensor for smart structures, including aerospace structures.

Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

Energy Technology Data Exchange (ETDEWEB)

Vognsen, Tina, E-mail: tv@farma.ku.dk [Biostructural Research, Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark); Kristensen, Ole, E-mail: ok@farma.ku.dk [Biostructural Research, Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)

2012-03-30

Highlights: Black-Right-Pointing-Pointer The crystal structure of the NTF2-like domain of Rasputin protein is presented. Black-Right-Pointing-Pointer Differences to known ligand binding sites of nuclear transport factor 2 are discussed. Black-Right-Pointing-Pointer A new ligand binding site for the Rasputin and G3BP proteins is proposed. -- Abstract: The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 A resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a {beta}-sheet and three {alpha}-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.

Characterization of high-power RF structures using time-domain field codes

International Nuclear Information System (INIS)

Shang, C.C.; DeFord, J.F.; Swatloski, T.L.

1992-01-01

We have modeled gyrotron windows and gyrotron amplifier sever structures for TE modes in the 100--150 GHz range and have computed the reflection and transmission characteristics from the field data. Good agreement with frequency domain codes and analytic analysis have been obtained for some simple geometries. We present results for realistic structures with lousy coatings and describe implementation of microwave diagnostics

Crystal structure of the second fibronectin type III (FN3) domain from human collagen α1 type XX.

Science.gov (United States)

Zhao, Jingfeng; Ren, Jixia; Wang, Nan; Cheng, Zhong; Yang, Runmei; Lin, Gen; Guo, Yi; Cai, Dayong; Xie, Yong; Zhao, Xiaohong

2017-12-01

Collagen α1 type XX, which contains fibronectin type III (FN3) repeats involving six FN3 domains (referred to as the FN#1-FN#6 domains), is an unusual member of the fibril-associated collagens with interrupted triple helices (FACIT) subfamily of collagens. The results of standard protein BLAST suggest that the FN3 repeats might contribute to collagen α1 type XX acting as a cytokine receptor. To date, solution NMR structures of the FN#3, FN#4 and FN#6 domains have been determined. To obtain further structural evidence to understand the relationship between the structure and function of the FN3 repeats from collagen α1 type XX, the crystal structure of the FN#2 domain from human collagen α1 type XX (residues Pro386-Pro466; referred to as FN2-HCXX) was solved at 2.5 Å resolution. The crystal structure of FN2-HCXX shows an immunoglobulin-like fold containing a β-sandwich structure, which is formed by a three-stranded β-sheet (β1, β2 and β5) packed onto a four-stranded β-sheet (β3, β4, β6 and β7). Two consensus domains, tencon and fibcon, are structural analogues of FN2-HCXX. Fn8, an FN3 domain from human oncofoetal fibronectin, is the closest structural analogue of FN2-HCXX derived from a naturally occurring sequence. Based solely on the structural similarity of FN2-HCXX to other FN3 domains, the detailed functions of FN2-HCXX and the FN3 repeats in collagen α1 type XX cannot be identified.

Drainage - Structure Correlation in tectonically active Regions: Case studies in the Bolivian and Colombian Andes

Science.gov (United States)

Zeilinger, Gerold; Parra, Mauricio; Kober, Florian

2017-04-01

Interandean Zone and the Subandean Zone (SA), exhibiting a catchment relief of up to 5000 m. While the structural trend in the EC is predominately NW-SE with a uniform (no preferred orientation) distribution of lower order fluvial channels, it changes in the SA into a distinct N-S trend with a pronounced E-W orientation of lower order fluvial channels. A similar pattern is recognized in the Eastern Andes of Colombia, where the structural trend is NE-SW. The Eastern Cordillera comprise a frontal thin-skinned Neogene and Paleogene domain (FR) and the more interior lower Cretaceous an Upper Paleozoic thick-skinned region (IR). The trend of higher order channels is, as expected, parallel to the structures in the interior parts and perpendicular in the frontal part. However, the trend of lower order channels reveal no directional correlation to the structural trend in the interior, but a significant correlation to the structures in the frontal range that suffered relatively to the interior domains younger deformation phases. We therefore postulate a dependency of the directional evolution of drainage patterns on the relative timing of tectonic activity. The only weakly preferred orientation of drainages in the interior parts (EC and IR) suggests a balance between structural control and drainage occupation, and higher maturity of the landscape. In contrast, the distinct pattern of drainages oblique to the structural grain in the frontal ranges (SA and FR) highlights the alignment of tributaries and suggests an ongoing tectonic control on drainage orientation. We test the hypothesis whether the correlation between the direction of small order rivers and the direction of structures can be used as a proxy for relative tectonic activity, which might be relevant in questions on 1) dominance of tectonics over climate, 2) dynamics of deformation propagation in fault-and-thrust-belts and 3) occurrence of higher erosion rates despite "limited" relief or threshold slopes. Ongoing efforts

Machine learning approaches to evaluate correlation patterns in allosteric signaling: A case study of the PDZ2 domain

Science.gov (United States)

Botlani, Mohsen; Siddiqui, Ahnaf; Varma, Sameer

2018-06-01

Many proteins are regulated by dynamic allostery wherein regulator-induced changes in structure are comparable with thermal fluctuations. Consequently, understanding their mechanisms requires assessment of relationships between and within conformational ensembles of different states. Here we show how machine learning based approaches can be used to simplify this high-dimensional data mining task and also obtain mechanistic insight. In particular, we use these approaches to investigate two fundamental questions in dynamic allostery. First, how do regulators modify inter-site correlations in conformational fluctuations (Cij)? Second, how are regulator-induced shifts in conformational ensembles at two different sites in a protein related to each other? We address these questions in the context of the human protein tyrosine phosphatase 1E's PDZ2 domain, which is a model protein for studying dynamic allostery. We use molecular dynamics to generate conformational ensembles of the PDZ2 domain in both the regulator-bound and regulator-free states. The employed protocol reproduces methyl deuterium order parameters from NMR. Results from unsupervised clustering of Cij combined with flow analyses of weighted graphs of Cij show that regulator binding significantly alters the global signaling network in the protein; however, not by altering the spatial arrangement of strongly interacting amino acid clusters but by modifying the connectivity between clusters. Additionally, we find that regulator-induced shifts in conformational ensembles, which we evaluate by repartitioning ensembles using supervised learning, are, in fact, correlated. This correlation Δij is less extensive compared to Cij, but in contrast to Cij, Δij depends inversely on the distance from the regulator binding site. Assuming that Δij is an indicator of the transduction of the regulatory signal leads to the conclusion that the regulatory signal weakens with distance from the regulatory site. Overall, this

Regulation of adhesion behavior of murine macrophage using supported lipid membranes displaying tunable mannose domains

International Nuclear Information System (INIS)

Kaindl, T; Oelke, J; Kaufmann, S; Tanaka, M; Pasc, A; Konovalov, O V; Funari, S S; Engel, U; Wixforth, A

2010-01-01

Highly uniform, strongly correlated domains of synthetically designed lipids can be incorporated into supported lipid membranes. The systematic characterization of membranes displaying a variety of domains revealed that the equilibrium size of domains significantly depends on the length of fluorocarbon chains, which can be quantitatively interpreted within the framework of an equivalent dipole model. A mono-dispersive, narrow size distribution of the domains enables us to treat the inter-domain correlations as two-dimensional colloidal crystallization and calculate the potentials of mean force. The obtained results demonstrated that both size and inter-domain correlation can precisely be controlled by the molecular structures. By coupling α-D-mannose to lipid head groups, we studied the adhesion behavior of the murine macrophage (J774A.1) on supported membranes. Specific adhesion and spreading of macrophages showed a clear dependence on the density of functional lipids. The obtained results suggest that such synthetic lipid domains can be used as a defined platform to study how cells sense the size and distribution of functional molecules during adhesion and spreading.

Role of structural inheritance on present-day deformation in intraplate domains

Science.gov (United States)

Tarayoun, A.; Mazzotti, S.; Gueydan, F.

2017-12-01

Understanding the role of structural inheritance on present day surface deformation is a key element for better characterizing the dynamism of intraplate earthquakes. Current deformation and seismicity are poorly understood phenomenon in intra-continental domains. A commonly used hypothesis, based on observations, suggests that intraplate deformation is related to the reactivation of large tectonic paleo-structures, which can act as locally weakened domains. The objective of our study is to quantify the impact of these weakened areas on present-day strain localizations and rates. We combine GPS observations and numerical modeling to analyze the role of structural inheritance on strain rates, with specific observations along the St. Lawrence Valley of eastern Canada. We processed 143 GPS stations from five different networks, in particular one dense campaign network situated along a recognized major normal faults system of the Iapetus paleo-rift, in order to accurately determine the GPS velocities and strain rates. Results of strain rates show magnitude varying from 1.5x10-10 to 6.8x10-9 yr-1 in the St Lawrence valley. Weakened area strain rates are up to one order of magnitude higher than surrounding areas. We compare strain rates inferred from GPS and the new postglacial rebound model. We found that GPS signal is one order of magnitude higher in the weakened zone, which is likely due to structural inheritance. The numerical modeling investigates the steady-state deformation of the continental lithosphere with presence of a weak area. Our new approach integrates ductile structural inheritance using a weakening coefficient that decreases the lithosphere strength at different depths. This allows studying crustal strain rates mainly as a function of rheological contrast and geometry of the weakened domains. Comparison between model predictions and observed GPS strain rates will allow us to investigate the respective role of crustal and mantle tectonic inheritance.

Molecular structures and functional relationships in clostridial neurotoxins.

Science.gov (United States)

Swaminathan, Subramanyam

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structures have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here. Journal compilation © 2011 FEBS. No claim to original US government works.

Structure of metabotropic glutamate receptor C-terminal domains in contact with interacting proteins

Directory of Open Access Journals (Sweden)

Ralf eEnz

2012-04-01

Full Text Available Metabotropic glutamate receptors (mGluRs regulate intracellular signal pathways that control several physiological tasks, including neuronal excitability, learning and memory. This is achieved by the formation of synaptic signal complexes, in which mGluRs assemble with functionally related proteins such as enzymes, scaffolds and cytoskeletal anchor proteins. Thus, mGluR associated proteins actively participate in the regulation of glutamatergic neurotransmission. Importantly, dysfunction of mGluRs and interacting proteins may lead to impaired signal transduction and finally result in neurological disorders, e.g. night blindness, addiction, epilepsy, schizophrenia, autism spectrum disorders and Parkinson´s disease. In contrast to solved crystal structures of extracellular N-terminal domains of some mGluR types, only a few studies analyzed the conformation of intracellular receptor domains. Intracellular C-termini of most mGluR types are subject to alternative splicing and can be further modified by phosphorylation and SUMOylation. In this way, diverse interaction sites for intracellular proteins that bind to and regulate the glutamate receptors are generated. Indeed, most of the known mGluR binding partners interact with the receptors´ C-terminal domains. Within the last years, different laboratories analyzed the structure of these domains and described the geometry of the contact surface between mGluR C-termini and interacting proteins. Here, I will review recent progress in the structure characterization of mGluR C-termini and provide an up-to-date summary of the geometry of these domains in contact with binding partners.

Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.

Science.gov (United States)

McDonald, Caleb B; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Lednev, Igor K; Farooq, Amjad

2013-01-01

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. Copyright © 2013 Elsevier B.V. All rights reserved.

Expression, purification and insights into structure and folding of the ADAM22 pro domain

DEFF Research Database (Denmark)

Sørensen, Hans Peter; Jacobsen, Jonas; Nielbo, Steen

2008-01-01

. To understand the functions of human ADAM pro domains and to determine three-dimensional structures, we have screened promising targets for expression and purification properties when using Escherichia coli as the host. The pro domain of ADAM22 (ADAM22-P) expressed in E. coli was folded, as determined by CD...... and NMR spectroscopy. An ADAM22-P fragment encoding residues 26-199 could be expressed in high amounts, remained soluble above 1 mM, and was suitable for structural studies by NMR spectroscopy. CD spectroscopy and predictions suggest that the secondary structure in ADAM22-P consists of beta...

Parallel iterative decoding of transform domain Wyner-Ziv video using cross bitplane correlation

DEFF Research Database (Denmark)

Luong, Huynh Van; Huang, Xin; Forchhammer, Søren

2011-01-01

decoding scheme is proposed to improve the coding efficiency of TDWZ video codecs. The proposed parallel iterative LDPC decoding scheme is able to utilize cross bitplane correlation during decoding, by iteratively refining the soft-input, updating a modeled noise distribution and thereafter enhancing......In recent years, Transform Domain Wyner-Ziv (TDWZ) video coding has been proposed as an efficient Distributed Video Coding (DVC) solution, which fully or partly exploits the source statistics at the decoder to reduce the computational burden at the encoder. In this paper, a parallel iterative LDPC...

Domain structures and magnetization reversal in Co/Pd and CoFeB/Pd multilayers

Energy Technology Data Exchange (ETDEWEB)

Sbiaa, R., E-mail: rachid@squ.edu.om [Department of Physics, Sultan Qaboos University, P.O. Box 36, PC 123 (Oman); Ranjbar, M. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Åkerman, J. [Physics Department, University of Gothenburg, 412 96 Gothenburg (Sweden); Materials Physics, School of ICT, Royal Institute of Technology (KTH), 164 40 Kista (Sweden)

2015-05-07

Domain structures and magnetization reversal of (Co/Pd) and (CoFeB/Pd) multilayers with 7 and 14 repeats were investigated. The Co-based multilayers show much larger coercivities, a better squareness, and a sharper magnetization switching than CoFeB-based multilayers. From magnetic force microscopy observations, both structures show strong reduction in domains size as the number of repeats increases but the magnetic domains for Co-based multilayers are more than one order of magnitude larger than for CoFeB-based multilayers. By imaging domains at different times, breaks in the (CoFeB/Pd) multilayer stripes were observed within only few hours, while no change could be seen for (Co/Pd) multilayers. Although CoFeB single layers are suitable for magnetoresistive devices due to their large spin polarization and low damping constants, their lamination with Pd suffers mainly from thermal instability.

Confirming the Revised C-Terminal Domain of the MscL Crystal Structure

OpenAIRE

Maurer, Joshua A.; Elmore, Donald E.; Clayton, Daniel; Xiong, Li; Lester, Henry A.; Dougherty, Dennis A.

2008-01-01

The structure of the C-terminal domain of the mechanosensitive channel of large conductance (MscL) has generated significant controversy. As a result, several structures have been proposed for this region: the original crystal structure (1MSL) of the Mycobacterium tuberculosis homolog (Tb), a model of the Escherichia coli homolog, and, most recently, a revised crystal structure of Tb-MscL (2OAR). To understand which of these structures represents a physiological conformation, we measured the ...

Structure of bacteriophage T4 fibritin: a segmented coiled coil and the role of the C-terminal domain.

Science.gov (United States)

Tao, Y; Strelkov, S V; Mesyanzhinov, V V; Rossmann, M G

1997-06-15

Oligomeric coiled-coil motifs are found in numerous protein structures; among them is fibritin, a structural protein of bacteriophage T4, which belongs to a class of chaperones that catalyze a specific phage-assembly process. Fibritin promotes the assembly of the long tail fibers and their subsequent attachment to the tail baseplate; it is also a sensing device that controls the retraction of the long tail fibers in adverse environments and, thus, prevents infection. The structure of fibritin had been predicted from sequence and biochemical analyses to be mainly a triple-helical coiled coil. The determination of its structure at atomic resolution was expected to give insights into the assembly process and biological function of fibritin, and the properties of modified coiled-coil structures in general. The three-dimensional structure of fibritin E, a deletion mutant of wild-type fibritin, was determined to 2.2 A resolution by X-ray crystallography. Three identical subunits of 119 amino acid residues form a trimeric parallel coiled-coil domain and a small globular C-terminal domain about a crystallographic threefold axis. The coiled-coil domain is divided into three segments that are separated by insertion loops. The C-terminal domain, which consists of 30 residues from each subunit, contains a beta-propeller-like structure with a hydrophobic interior. The residues within the C-terminal domain make extensive hydrophobic and some polar intersubunit interactions. This is consistent with the C-terminal domain being important for the correct assembly of fibritin, as shown earlier by mutational studies. Tight interactions between the C-terminal residues of adjacent subunits counteract the latent instability that is suggested by the structural properties of the coiled-coil segments. Trimerization is likely to begin with the formation of the C-terminal domain which subsequently initiates the assembly of the coiled coil. The interplay between the stabilizing effect of the C

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.

High-resolution crystal structure reveals a HEPN domain at the C-terminal region of S. cerevisiae RNA endonuclease Swt1

International Nuclear Information System (INIS)

Peng, Shuxia; Zhou, Ke; Wang, Wenjia; Gao, Zengqiang; Dong, Yuhui; Liu, Quansheng

2014-01-01

Highlights: • Crystal structure of the C-terminal (CT) domain of Swt1 was determined at 2.3 Å. • Structure of the CT domain was identified as HEPN domain superfamily member. • Low-resolution envelope of Swt1 full-length in solution was analyzed by SAXS. • The middle and CT domains gave good fit to SAXS structural model. - Abstract: Swt1 is an RNA endonuclease that plays an important role in quality control of nuclear messenger ribonucleoprotein particles (mRNPs) in eukaryotes; however, its structural details remain to be elucidated. Here, we report the crystal structure of the C-terminal (CT) domain of Swt1 from Saccharomyces cerevisiae, which shares common characteristics of higher eukaryotes and prokaryotes nucleotide binding (HEPN) domain superfamily. To study in detail the full-length protein structure, we analyzed the low-resolution architecture of Swt1 in solution using small angle X-ray scattering (SAXS) method. Both the CT domain and middle domain exhibited a good fit upon superimposing onto the molecular envelope of Swt1. Our study provides the necessary structural information for detailed analysis of the functional role of Swt1, and its importance in the process of nuclear mRNP surveillance

Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.

Science.gov (United States)

Gong, Xin; Qian, Hongwu; Shao, Wei; Li, Jingxian; Wu, Jianping; Liu, Jun-Jie; Li, Wenqi; Wang, Hong-Wei; Espenshade, Peter; Yan, Nieng

2016-11-01

Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 Å and cryo-EM structure of the complex at 5.4 Å together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.

Differences between time domain and Fourier domain optical coherence tomography in imaging tissues.

Science.gov (United States)

Gao, W; Wu, X

2017-11-01

It has been numerously demonstrated that both time domain and Fourier domain optical coherence tomography (OCT) can generate high-resolution depth-resolved images of living tissues and cells. In this work, we compare the common points and differences between two methods when the continuous and random properties of live tissue are taken into account. It is found that when relationships that exist between the scattered light and tissue structures are taken into account, spectral interference measurements in Fourier domain OCT (FDOCT) is more advantageous than interference fringe envelope measurements in time domain OCT (TDOCT) in the cases where continuous property of tissue is taken into account. It is also demonstrated that when random property of tissue is taken into account FDOCT measures the Fourier transform of the spatial correlation function of the refractive index and speckle phenomena will limit the effective limiting imaging resolution in both TDOCT and FDOCT. Finally, the effective limiting resolution of both TDOCT and FDOCT are given which can be used to estimate the effective limiting resolution in various practical applications. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Structure of the Escherichia coli RNA polymerase α subunit C-terminal domain

International Nuclear Information System (INIS)

Lara-González, Samuel; Birktoft, Jens J.; Lawson, Catherine L.

2010-01-01

The crystal structure of the dimethyllysine derivative of the E. coli RNA polymerase α subunit C-terminal domain is reported at 2.0 Å resolution. The α subunit C-terminal domain (αCTD) of RNA polymerase (RNAP) is a key element in transcription activation in Escherichia coli, possessing determinants responsible for the interaction of RNAP with DNA and with transcription factors. Here, the crystal structure of E. coli αCTD (α subunit residues 245–329) determined to 2.0 Å resolution is reported. Crystals were obtained after reductive methylation of the recombinantly expressed domain. The crystals belonged to space group P2 1 and possessed both pseudo-translational symmetry and pseudo-merohedral twinning. The refined coordinate model (R factor = 0.193, R free = 0.236) has improved geometry compared with prior lower resolution determinations of the αCTD structure [Jeon et al. (1995 ▶), Science, 270, 1495–1497; Benoff et al. (2002 ▶), Science, 297, 1562–1566]. An extensive dimerization interface formed primarily by N- and C-terminal residues is also observed. The new coordinates will facilitate the improved modeling of αCTD-containing multi-component complexes visualized at lower resolution using X-ray crystallography and electron-microscopy reconstruction

Characterization of high-power RF structures using time-domain field codes

International Nuclear Information System (INIS)

Shang, C.C.; DeFord, J.F.; Swatloski, T.L.

1992-01-01

We have modeled gyrotron windows and gyrotron amplifier sever structures for TE modes in the 100-150 GHz range and have computed the reflection and transmission characteristics from the field data. Good agreement with frequency domain codes and analytic analysis have been obtained for some simple geometries. We present results for realistic structures with lossy coatings and describe implementation of microwave diagnostics. (Author) 5 figs., 7 refs

Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling.

Science.gov (United States)

Mas, Caroline; Norwood, Suzanne J; Bugarcic, Andrea; Kinna, Genevieve; Leneva, Natalya; Kovtun, Oleksiy; Ghai, Rajesh; Ona Yanez, Lorena E; Davis, Jasmine L; Teasdale, Rohan D; Collins, Brett M

2014-10-10

Sorting nexins (SNXs) or phox homology (PX) domain containing proteins are central regulators of cell trafficking and signaling. A subfamily of PX domain proteins possesses two unique PX-associated domains, as well as a regulator of G protein-coupled receptor signaling (RGS) domain that attenuates Gαs-coupled G protein-coupled receptor signaling. Here we delineate the structural organization of these RGS-PX proteins, revealing a protein family with a modular architecture that is conserved in all eukaryotes. The one exception to this is mammalian SNX19, which lacks the typical RGS structure but preserves all other domains. The PX domain is a sensor of membrane phosphoinositide lipids and we find that specific sequence alterations in the PX domains of the mammalian RGS-PX proteins, SNX13, SNX14, SNX19, and SNX25, confer differential phosphoinositide binding preferences. Although SNX13 and SNX19 PX domains bind the early endosomal lipid phosphatidylinositol 3-phosphate, SNX14 shows no membrane binding at all. Crystal structures of the SNX19 and SNX14 PX domains reveal key differences, with alterations in SNX14 leading to closure of the binding pocket to prevent phosphoinositide association. Our findings suggest a role for alternative membrane interactions in spatial control of RGS-PX proteins in cell signaling and trafficking. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

The influence of punching process on residual stress and magnetic domain structure of non-oriented silicon steel

International Nuclear Information System (INIS)

Cao, Hongzhi; Hao, Linpo; Yi, Jingwen; Zhang, Xianglin; Luo, Zhonghan; Chen, Shenglin; Li, Rongfeng

2016-01-01

The main purpose of this paper is to investigate the influence of punching process on residual stress and magnetic domain structure. The residual stress in non-oriented silicon steel after punching process was measured by nanoindentation. The maximum depth was kept constant as 300 nm during nanoindentation. The material around indentation region exhibited no significant pile-up deformation. The calculation of residual stress was based on the Suresh theoretical model. Our experimental results show that residual compressive stress was generated around the sheared edge after punching. The width of residual stress affected zone by punching was around 0.4–0.5 mm. After annealing treatment, the residual stress was significantly decreased. Magnetic domain structure was observed according to the Bitter method. The un-annealed sample exhibited complicated domain patterns, and the widths of the magnetic domains varied between 3 µm and 8 µm. Most of the domain patterns of the annealed sample were 180°-domains and 90°-domains, and the widths of the domains decreased to 1–3 µm. - Highlights: • The residual stress distribution on sheared edge was measured. • The residual compressive stress was generated around the sheared edge. • The width of residual stress affected zone was about 0.4–0.5 mm. • The shape and width of the domain structure would be changed by annealing.

Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.

Science.gov (United States)

Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek

2016-11-20

The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-α receptor and TYK2. Published by Elsevier Ltd.

Solution structure of GSP13 from Bacillus subtilis exhibits an S1 domain related to cold shock proteins

International Nuclear Information System (INIS)

Yu Wenyu; Hu Jicheng; Yu Bingke; Xia Wei; Jin Changwen; Xia Bin

2009-01-01

GSP13 encoded by gene yugI is a σ B -dependent general stress protein in Bacillus subtilis, which can be induced by heat shock, salt stress, ethanol stress, glucose starvation, oxidative stress and cold shock. Here we report the solution structure of GSP13 and it is the first structure of S1 domain containing protein in Bacillus subtilis. The structure of GSP13 mainly consists of a typical S1 domain along with a C-terminal 50-residue flexible tail, different from the other known S1 domain containing proteins. Comparison with other S1 domain structures reveals that GSP13 has a conserved RNA binding surface, and it may function similarly to cold shock proteins in response to cold stress

Elasticity Imaging of Ferroelectric Domain Structure in PZT by Ultrasonic Atomic Force Microscopy

International Nuclear Information System (INIS)

Tsuji, T.; Ogiso, H.; Fukuda, K.; Yamanaka, K.

2004-01-01

UAFM was applied to the observation of the domain structure in lead zirconate titanate (PZT). It imaged the change of elasticity due to grain and domain boundary (DB). For the quantitative evaluation of the contact stiffness, the lateral contact stiffness was taken into account. The stiffness of DB was 10% lower than that within the domain and the width of the DB was about 30 nm. The implication of this work is the understanding of the fatigue mechanism in a PZT memory and the high resolution imaging for a high-density memory

Sequence and structural analysis of the chitinase insertion domain reveals two conserved motifs involved in chitin-binding.

Directory of Open Access Journals (Sweden)

Hai Li

2010-01-01

Full Text Available Chitinases are prevalent in life and are found in species including archaea, bacteria, fungi, plants, and animals. They break down chitin, which is the second most abundant carbohydrate in nature after cellulose. Hence, they are important for maintaining a balance between carbon and nitrogen trapped as insoluble chitin in biomass. Chitinases are classified into two families, 18 and 19 glycoside hydrolases. In addition to a catalytic domain, which is a triosephosphate isomerase barrel, many family 18 chitinases contain another module, i.e., chitinase insertion domain. While numerous studies focus on the biological role of the catalytic domain in chitinase activity, the function of the chitinase insertion domain is not completely understood. Bioinformatics offers an important avenue in which to facilitate understanding the role of residues within the chitinase insertion domain in chitinase function.Twenty-seven chitinase insertion domain sequences, which include four experimentally determined structures and span five kingdoms, were aligned and analyzed using a modified sequence entropy parameter. Thirty-two positions with conserved residues were identified. The role of these conserved residues was explored by conducting a structural analysis of a number of holo-enzymes. Hydrogen bonding and van der Waals calculations revealed a distinct subset of four conserved residues constituting two sequence motifs that interact with oligosaccharides. The other conserved residues may be key to the structure, folding, and stability of this domain.Sequence and structural studies of the chitinase insertion domains conducted within the framework of evolution identified four conserved residues which clearly interact with the substrates. Furthermore, evolutionary studies propose a link between the appearance of the chitinase insertion domain and the function of family 18 chitinases in the subfamily A.

Quantifying NMR relaxation correlation and exchange in articular cartilage with time domain analysis

Science.gov (United States)

Mailhiot, Sarah E.; Zong, Fangrong; Maneval, James E.; June, Ronald K.; Galvosas, Petrik; Seymour, Joseph D.

2018-02-01

Measured nuclear magnetic resonance (NMR) transverse relaxation data in articular cartilage has been shown to be multi-exponential and correlated to the health of the tissue. The observed relaxation rates are dependent on experimental parameters such as solvent, data acquisition methods, data analysis methods, and alignment to the magnetic field. In this study, we show that diffusive exchange occurs in porcine articular cartilage and impacts the observed relaxation rates in T1-T2 correlation experiments. By using time domain analysis of T2-T2 exchange spectroscopy, the diffusive exchange time can be quantified by measurements that use a single mixing time. Measured characteristic times for exchange are commensurate with T1 in this material and so impacts the observed T1 behavior. The approach used here allows for reliable quantification of NMR relaxation behavior in cartilage in the presence of diffusive fluid exchange between two environments.

The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.

Science.gov (United States)

Kamajaya, Aron; Kaiser, Jens T; Lee, Jonas; Reid, Michelle; Rees, Douglas C

2014-10-07

Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnetic domain structures and stray fields of individual elongated magnetite grains revealed by magnetic force microscopy (MFM)

DEFF Research Database (Denmark)

Frandsen, Cathrine; Stipp, S. L. S.; McEnroe, S. A.

2004-01-01

), the internal domain structure was determined for individual grains. In general, the lamellae were pseudo-single-domain grains with open-flux domain magnetisations parallel to their long axes. The domain sizes were, in cross-section, on the order of a micrometer for the longer lamellae and about 300 nm...

Structure-function analysis of the OB and latch domains of chlorella virus DNA ligase.

Science.gov (United States)

Samai, Poulami; Shuman, Stewart

2011-06-24

Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5'-phosphate nucleotide and the 3'-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps.

Structure-Function Analysis of the OB and Latch Domains of Chlorella Virus DNA Ligase*

Science.gov (United States)

Samai, Poulami; Shuman, Stewart

2011-01-01

Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5′-phosphate nucleotide and the 3′-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps. PMID:21527793

Structure determination of the functional domain interaction of a chimeric nonribosomal peptide synthetase from a challenging crystal with noncrystallographic translational symmetry

Energy Technology Data Exchange (ETDEWEB)

Sundlov, Jesse A.; Gulick, Andrew M., E-mail: gulick@hwi.buffalo.edu [University at Buffalo, 700 Ellicott Street, Buffalo, NY 14203 (United States)

2013-08-01

The structure of the functional interaction of NRPS adenylation and carrier protein domains, trapped with a mechanism-based inhibitor, is described. Crystals exhibit translational non-crystallographic symmetry, which challenged structure determination and refinement. The nonribosomal peptide synthetases (NRPSs) are a family of modular proteins that contain multiple catalytic domains joined in a single protein. Together, these domains work to produce chemically diverse peptides, including compounds with antibiotic activity or that play a role in iron acquisition. Understanding the structural mechanisms that govern the domain interactions has been a long-standing goal. During NRPS synthesis, amino-acid substrates are loaded onto integrated carrier protein domains through the activity of NRPS adenylation domains. The structures of two adenylation domain–carrier protein domain complexes have recently been determined in an effort that required the use of a mechanism-based inhibitor to trap the domain interaction. Here, the continued analysis of these proteins is presented, including a higher resolution structure of an engineered di-domain protein containing the EntE adenylation domain fused with the carrier protein domain of its partner EntB. The protein crystallized in a novel space group in which molecular replacement and refinement were challenged by noncrystallographic pseudo-translational symmetry. The structure determination and how the molecular packing impacted the diffraction intensities are reported. Importantly, the structure illustrates that in this new crystal form the functional interface between the adenylation domain and the carrier protein domain remains the same as that observed previously. At a resolution that allows inclusion of water molecules, additional interactions are observed between the two protein domains and between the protein and its ligands. In particular, a highly solvated region that surrounds the carrier protein cofactor is described.

Structure determination of the functional domain interaction of a chimeric nonribosomal peptide synthetase from a challenging crystal with noncrystallographic translational symmetry

International Nuclear Information System (INIS)

Sundlov, Jesse A.; Gulick, Andrew M.

2013-01-01

The structure of the functional interaction of NRPS adenylation and carrier protein domains, trapped with a mechanism-based inhibitor, is described. Crystals exhibit translational non-crystallographic symmetry, which challenged structure determination and refinement. The nonribosomal peptide synthetases (NRPSs) are a family of modular proteins that contain multiple catalytic domains joined in a single protein. Together, these domains work to produce chemically diverse peptides, including compounds with antibiotic activity or that play a role in iron acquisition. Understanding the structural mechanisms that govern the domain interactions has been a long-standing goal. During NRPS synthesis, amino-acid substrates are loaded onto integrated carrier protein domains through the activity of NRPS adenylation domains. The structures of two adenylation domain–carrier protein domain complexes have recently been determined in an effort that required the use of a mechanism-based inhibitor to trap the domain interaction. Here, the continued analysis of these proteins is presented, including a higher resolution structure of an engineered di-domain protein containing the EntE adenylation domain fused with the carrier protein domain of its partner EntB. The protein crystallized in a novel space group in which molecular replacement and refinement were challenged by noncrystallographic pseudo-translational symmetry. The structure determination and how the molecular packing impacted the diffraction intensities are reported. Importantly, the structure illustrates that in this new crystal form the functional interface between the adenylation domain and the carrier protein domain remains the same as that observed previously. At a resolution that allows inclusion of water molecules, additional interactions are observed between the two protein domains and between the protein and its ligands. In particular, a highly solvated region that surrounds the carrier protein cofactor is described

Anti-correlation and subsector structure in financial systems

Science.gov (United States)

Jiang, X. F.; Zheng, B.

2012-02-01

With the random matrix theory, we study the spatial structure of the Chinese stock market, the American stock market and global market indices. After taking into account the signs of the components in the eigenvectors of the cross-correlation matrix, we detect the subsector structure of the financial systems. The positive and negative subsectors are anti-correlated with respect to each other in the corresponding eigenmode. The subsector structure is strong in the Chinese stock market, while somewhat weaker in the American stock market and global market indices. Characteristics of the subsector structures in different markets are revealed.

Time-varying correlation and common structures in volatility

NARCIS (Netherlands)

Liu, Yang

2016-01-01

This thesis studies time series properties of the covariance structure of multivariate asset returns. First, the time-varying feature of correlation is investigated at the intraday level with a new correlation model incorporating the intraday correlation dynamics. Second, the thesis develops a

The BARD1 C-Terminal Domain Structure and Interactions with Polyadenylation Factor CstF-50

Energy Technology Data Exchange (ETDEWEB)

Edwards, Ross A.; Lee, Megan S.; Tsutakawa, Susan E.; Williams, R. Scott; Tainer, John A.; Glover, J. N. Mark

2009-07-13

The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF- 50 binding. The crystal structure of the BARD1 BRCT domain uncovers a degenerate phosphopeptide binding pocket lacking the key arginine required for phosphopeptide interactions in other BRCT proteins.Small angle X-ray scattering together with limited proteolysis results indicates that ankyrin and BRCT domains are linked by a flexible tether and do not adopt a fixed orientation relative to one another. Protein pull-down experiments utilizing a series of purified BARD1 deletion mutants indicate that interactions between the CstF-50 WD-40 domain and BARD1 involve the ankyrin-BRCT linker but do not require ankyrin or BRCT domains. The structural plasticity imparted by the ANK-BRCT linker helps to explain the regulated assembly of different protein BARD1 complexes with distinct functions in DNA damage signaling including BARD1-dependent induction of apoptosis plus p53 stabilization and interactions. BARD1 architecture and plasticity imparted by the ANK-BRCT linker are suitable to allow the BARD1 C-terminus to act as a hub with multiple binding sites to integrate diverse DNA damage signals directly to RNA polymerase.

Interaction of the p85 subunit of PI 3-kinase and its N-terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes.

Science.gov (United States)

Panayotou, G; Bax, B; Gout, I; Federwisch, M; Wroblowski, B; Dhand, R; Fry, M J; Blundell, T L; Wollmer, A; Waterfield, M D

1992-01-01

Circular dichroism and fluorescence spectroscopy were used to investigate the structure of the p85 alpha subunit of the PI 3-kinase, a closely related p85 beta protein, and a recombinant SH2 domain-containing fragment of p85 alpha. Significant spectral changes, indicative of a conformational change, were observed on formation of a complex with a 17 residue peptide containing a phosphorylated tyrosine residue. The sequence of this peptide is identical to the sequence surrounding Tyr751 in the kinase-insert region of the platelet-derived growth factor beta-receptor (beta PDGFR). The rotational correlation times measured by fluorescence anisotropy decay indicated that phosphopeptide binding changed the shape of the SH2 domain-containing fragment. The CD and fluorescence spectroscopy data support the secondary structure prediction based on sequence analysis and provide evidence for flexible linker regions between the various domains of the p85 proteins. The significance of these results for SH2 domain-containing proteins is discussed. Images PMID:1330535

Bifurcation Observation of Combining Spiral Gear Transmission Based on Parameter Domain Structure Analysis

Directory of Open Access Journals (Sweden)

He Lin

2016-01-01

Full Text Available This study considers the bifurcation evolutions for a combining spiral gear transmission through parameter domain structure analysis. The system nonlinear vibration equations are created with piecewise backlash and general errors. Gill’s numerical integration algorithm is implemented in calculating the vibration equation sets. Based on cell-mapping method (CMM, two-dimensional dynamic domain planes have been developed and primarily focused on the parameters of backlash, transmission error, mesh frequency and damping ratio, and so forth. Solution demonstrates that Period-doubling bifurcation happens as the mesh frequency increases; moreover nonlinear discontinuous jump breaks the periodic orbit and also turns the periodic state into chaos suddenly. In transmission error planes, three cell groups which are Period-1, Period-4, and Chaos have been observed, and the boundary cells are the sensitive areas to dynamic response. Considering the parameter planes which consist of damping ratio associated with backlash, transmission error, mesh stiffness, and external load, the solution domain structure reveals that the system step into chaos undergoes Period-doubling cascade with Period-2m (m: integer periodic regions. Direct simulations to obtain the bifurcation diagram and largest Lyapunov exponent (LE match satisfactorily with the parameter domain solutions.

Investigating potential correlations between jet engine noise and plume dynamics in the hypertemporal infrared domain

Science.gov (United States)

Cunio, Phillip M.; Weber, Reed; Knobel, Kimberly; Wager, Jason; Lopez, Gerardo

2014-09-01

Jet engine noise can be a hazard and environmental pollutant, affecting personnel working in close proximity to jet engines. Mitigating the effects of jet engine noise could reduce the potential for hearing loss in runway workers, but engine noise is not yet sufficiently well-characterized that it can easily be mitigated for new engine designs. That is, there exists a very complex relationship between jet engine design parameters, operating conditions, and resultant noise power levels. In this paper, we propose to evaluate the utility of high-speed imaging (also called hypertemporal imaging) in correlating the infrared signatures of jet aircraft engines with acoustic noise from the jet engines. This paper will focus on a theoretical analysis of jet engine infrared signatures, and will define potentially-detectable characteristics of such signatures in the hypertemporal domain. A systematic test campaign to determine whether such signatures actually exist and can be correlated with acoustic jet engine characteristics will be proposed. The detection of any hypertemporal signatures in association with acoustic signatures of jet engines will enable the use of a new domain in characterizing jet engine noise. This may in turn enable new methods of predicting or mitigating jet engine noise, which could lead to benefits for operators of large numbers of jet engines.

A Review of Domain Modelling and Domain Imaging Techniques in Ferroelectric Crystals

Directory of Open Access Journals (Sweden)

John E. Huber

2011-02-01

Full Text Available The present paper reviews models of domain structure in ferroelectric crystals, thin films and bulk materials. Common crystal structures in ferroelectric materials are described and the theory of compatible domain patterns is introduced. Applications to multi-rank laminates are presented. Alternative models employing phase-field and related techniques are reviewed. The paper then presents methods of observing ferroelectric domain structure, including optical, polarized light, scanning electron microscopy, X-ray and neutron diffraction, atomic force microscopy and piezo-force microscopy. Use of more than one technique for unambiguous identification of the domain structure is also described.

Neural correlates of cross-domain affective priming.

Science.gov (United States)

Zhang, Qin; Li, Xiaohua; Gold, Brian T; Jiang, Yang

2010-05-06

The affective priming effect has mostly been studied using reaction time (RT) measures; however, the neural bases of affective priming are not well established. To understand the neural correlates of cross-domain emotional stimuli presented rapidly, we obtained event-related potential (ERP) measures during an affective priming task using short SOA (stimulus onset asynchrony) conditions. Two sets of 480 picture-word pairs were presented at SOAs of either 150ms or 250ms between prime and target stimuli. Participants decided whether the valence of each target word was pleasant or unpleasant. Behavioral results from both SOA conditions were consistent with previous reports of affective priming, with longer RTs for incongruent than congruent pairs at SOAs of 150ms (771 vs. 738ms) and 250ms (765 vs. 720ms). ERP results revealed that the N400 effect (associated with incongruent pairs in affective processing) occurred at anterior scalp regions at an SOA of 150ms, and this effect was only observed for negative target words across the scalp at an SOA of 250ms. In contrast, late positive potentials (LPPs) (associated with attentional resource allocation) occurred across the scalp at an SOA of 250ms. LPPs were only observed for positive target words at posterior parts of the brain at an SOA of 150ms. Our finding of ERP signatures at very short SOAs provides the first neural evidence that affective pictures can exert an automatic influence on the evaluation of affective target words. Copyright 2010 Elsevier B.V. All rights reserved.

Purification of SOCS (Suppressor of Cytokine Signaling) SH2 Domains for Structural and Functional Studies.

Science.gov (United States)

Liau, Nicholas P D; Laktyushin, Artem; Babon, Jeffrey J

2017-01-01

Src Homology 2 (SH2) domains are protein domains which have a high binding affinity for specific amino acid sequences containing a phosphorylated tyrosine residue. The Suppressors of Cytokine Signaling (SOCS) proteins use an SH2 domain to bind to components of certain cytokine signaling pathways to downregulate the signaling cascade. The recombinantly produced SH2 domains of various SOCS proteins have been used to undertake structural and functional studies elucidating the method of how such targeting occurs. Here, we describe the protocol for the recombinant production and purification of SOCS SH2 domains, with an emphasis on SOCS3.

The impact of domain knowledge on structured data collection and templated note design.

Science.gov (United States)

Windle, T; McClay, J C; Windle, J R

2013-01-01

The objective of this case report is to evaluate the importance of specialized domain knowledge when designing and using structured templated notes in a clinical environment. To analyze the impact of specialization on structured note generation we compared notes generated for three scenarios: 1) We compared the templated history of present illness (HPI) for patients presenting with a dermatology concern to the dermatologist versus the emergency department. 2) We compared the evaluation of chest pain by ED physicians versus cardiologists. 3) Finally, we compared the data elements asked for in the evaluation of the gastrointestinal system between cardiologists and the liver transplant service (LTS). We used the SNOMED CT representation via BioPortal to evaluate specificity and grouping between data elements and specialized physician groups. We found few similarities in structured data elements designed by and for the specific physician groups. The distinctness represented both differences in granularity as well as fundamental differences in data elements requested. When compared to ED physicians, dermatologists had different and more granular elements while cardiologists requested much more granular data. Comparing cardiologists and LTS, there were differences in the data elements requested. This case study supports the importance of domain knowledge in EHR design and implementation. That different specialities should want and use different information is well supported by cognitive science literature. Despite this, it is rare for domain knowledge to be considered in EHR implementation. Physicians with correct domain knowledge should be involved in the design process of templated notes.

Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

DEFF Research Database (Denmark)

Vognsen, Tina Reinholdt; Kristensen, Ole

2012-01-01

The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a ß-sheet and three a-helices forming...

Monte Carlo Simulation of Ferroelectric Domain Structure and Applied Field Response in Two Dimensions

Energy Technology Data Exchange (ETDEWEB)

Potter, Jr., B.G.; Tikare, V.; Tuttle, B.A.

1999-06-30

A 2-D, lattice-Monte Carlo approach was developed to simulate ferroelectric domain structure. The model currently utilizes a Hamiltonian for the total energy based only upon electrostatic terms involving dipole-dipole interactions, local polarization gradients and the influence of applied electric fields. The impact of boundary conditions on the domain configurations obtained was also examined. In general, the model exhibits domain structure characteristics consistent with those observed in a tetragonally distorted ferroelectric. The model was also extended to enable the simulation of ferroelectric hysteresis behavior. Simulated hysteresis loops were found to be very similar in appearance to those observed experimentally in actual materials. This qualitative agreement between the simulated hysteresis loop characteristics and real ferroelectric behavior was also confirmed in simulations run over a range of simulation temperatures and applied field frequencies.

Crystal structure of the C-terminal domain of the RAP74 subunit of human transcription factor IIF

Energy Technology Data Exchange (ETDEWEB)

Kamada, Katsuhiko; De Angelis, Jacqueline; Roeder, Robert G.; Burley, Stephen K. (Rockefeller)

2012-12-13

The x-ray structure of a C-terminal fragment of the RAP74 subunit of human transcription factor (TF) IIF has been determined at 1.02-{angstrom} resolution. The {alpha}/{beta} structure is strikingly similar to the globular domain of linker histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3{gamma} (HNF-3{gamma}), making it a winged-helix protein. The surface electrostatic properties of this compact domain differ significantly from those of bona fide winged-helix transcription factors (HNF-3{gamma} and RFX1) and from the winged-helix domains found within the RAP30 subunit of TFIIF and the {beta} subunit of TFIIE. RAP74 has been shown to interact with the TFIIF-associated C-terminal domain phosphatase FCP1, and a putative phosphatase binding site has been identified within the RAP74 winged-helix domain.

Magneto-optics observation of spontaneous domain structure in ferromagnetic La0.78Ca0.22MnO3 single crystal

International Nuclear Information System (INIS)

Jung, G; Indenbom, M; Markovich, V; Beek, C J van der; Mogilyansky, D; Mukovskii, Ya M

2004-01-01

Spontaneous ferromagnetic domains in lightly Ca-doped La 1-x Ca x MnO 3 single crystals have been visualized and investigated by means of the magneto-optical technique. In marked difference to the magnetic contrast structures associated with magneto-crystalline anisotropy, which appear only in applied magnetic field, spontaneous ferromagnetic domains show up at low temperatures below the Curie temperature in zero applied field and are characterized by oppositely oriented spontaneous magnetization in adjacent domains. Ferromagnetic domains seen in zero field cooled samples take the form of almost periodic, corrugated stripe-like structures. Application of even a very weak magnetic field during cooling through the magnetic ordering transition changes the stripe domain structures into a bubble domain system

Solution structure and dynamics of C-terminal regulatory domain of Vibrio vulnificus extracellular metalloprotease

Energy Technology Data Exchange (ETDEWEB)

Yun, Ji-Hye; Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Park, Jung Eun [Department of Biotechnology, College of Natural Sciences, Chosun University, Gwangju 501-759 (Korea, Republic of); Lee, Jung Sup, E-mail: jsplee@mail.chosun.ac.kr [Department of Biotechnology, College of Natural Sciences, Chosun University, Gwangju 501-759 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2013-01-11

Highlights: Black-Right-Pointing-Pointer We have determined solution structures of vEP C-terminal regulatory domain. Black-Right-Pointing-Pointer vEP C-ter100 has a compact {beta}-barrel structure with eight anti-parallel {beta}-strands. Black-Right-Pointing-Pointer Solution structure of vEP C-ter100 shares its molecular topology with that of the collagen-binding domain of collagenase. Black-Right-Pointing-Pointer Residues in the {beta}3 region of vEP C-ter100 might be important in putative ligand/receptor binding. Black-Right-Pointing-Pointer vEP C-ter100 interacts strongly with iron ion. -- Abstract: An extracellular metalloprotease (vEP) secreted by Vibrio vulnificus ATCC29307 is a 45-kDa proteolytic enzyme that has prothrombin activation and fibrinolytic activities during bacterial infection. The action of vEP could result in clotting that could serve to protect the bacteria from the host defense machinery. Very recently, we showed that the C-terminal propeptide (C-ter100), which is unique to vEP, is involved in regulation of vEP activity. To understand the structural basis of this function of vEP C-ter100, we have determined the solution structure and backbone dynamics using multidimensional nuclear magnetic resonance spectroscopy. The solution structure shows that vEP C-ter100 is composed of eight anti-parallel {beta}-strands with a unique fold that has a compact {beta}-barrel formation which stabilized by hydrophobic and hydrogen bonding networks. Protein dynamics shows that the overall structure, including loops, is very rigid and stabilized. By structural database analysis, we found that vEP C-ter100 shares its topology with that of the collagen-binding domain of collagenase, despite low sequence homology between the two domains. Fluorescence assay reveals that vEP C-ter100 interacts strongly with iron (Fe{sup 3+}). These findings suggest that vEP protease might recruit substrate molecules, such as collagen, by binding at C-ter100 and that vEP participates

Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase.

Science.gov (United States)

Meiselbach, Heike; Sticht, Heinrich

2011-08-01

The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function despite their high overall structural similarity. In this context, the differences in the SH3-SH2 domain linkers might play a role for differential regulation, but the structural consequences of linker sequence remain poorly understood. We have therefore performed comparative molecular dynamics simulations of wildtype Hck and of a mutant Hck in which the SH3-SH2 domain linker is replaced by the corresponding sequence from the homologous kinase Lck. These simulations reveal that linker replacement not only affects the orientation of the SH3 domain itself, but also leads to an alternative conformation of the activation segment in the Hck kinase domain. The sequence of the SH3-SH2 domain linker thus exerts a remote effect on the active site geometry and might therefore play a role in modulating the structure of the inactive kinase or in fine-tuning the activation process itself.

Protein structure recognition: From eigenvector analysis to structural threading method

Science.gov (United States)

Cao, Haibo

In this work, we try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. We found a strong correlation between amino acid sequence and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, we give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part include discussions of interactions among amino acids residues, lattice HP model, and the designablity principle. In the second part, we try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in our eigenvector study of protein contact matrix. We believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, we discuss a threading method based on the correlation between amino acid sequence and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, we list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

Protein Structure Recognition: From Eigenvector Analysis to Structural Threading Method

Energy Technology Data Exchange (ETDEWEB)

Cao, Haibo [Iowa State Univ., Ames, IA (United States)

2003-01-01

In this work, they try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. They found a strong correlation between amino acid sequences and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, they give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part includes discussions of interactions among amino acids residues, lattice HP model, and the design ability principle. In the second part, they try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in the eigenvector study of protein contact matrix. They believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, they discuss a threading method based on the correlation between amino acid sequences and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, they list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

Protein Structure Recognition: From Eigenvector Analysis to Structural Threading Method

International Nuclear Information System (INIS)

Haibo Cao

2003-01-01

In this work, they try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. They found a strong correlation between amino acid sequences and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, they give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part includes discussions of interactions among amino acids residues, lattice HP model, and the design ability principle. In the second part, they try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in the eigenvector study of protein contact matrix. They believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, they discuss a threading method based on the correlation between amino acid sequences and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, they list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches

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

Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily.

Science.gov (United States)

Nelson, Christopher A; Epperson, Megan L; Singh, Sukrit; Elliott, Jabari I; Fremont, Daved H

2015-08-28

Poxviruses encode a broad array of proteins that serve to undermine host immune defenses. Structural analysis of four of these seemingly unrelated proteins revealed the recurrent use of a conserved beta-sandwich fold that has not been observed in any eukaryotic or prokaryotic protein. Herein we propose to call this unique structural scaffolding the PIE (Poxvirus Immune Evasion) domain. PIE domain containing proteins are abundant in chordopoxvirinae, with our analysis identifying 20 likely PIE subfamilies among 33 representative genomes spanning 7 genera. For example, cowpox strain Brighton Red appears to encode 10 different PIEs: vCCI, A41, C8, M2, T4 (CPVX203), and the SECRET proteins CrmB, CrmD, SCP-1, SCP-2, and SCP-3. Characterized PIE proteins all appear to be nonessential for virus replication, and all contain signal peptides for targeting to the secretory pathway. The PIE subfamilies differ primarily in the number, size, and location of structural embellishments to the beta-sandwich core that confer unique functional specificities. Reported ligands include chemokines, GM-CSF, IL-2, MHC class I, and glycosaminoglycans. We expect that the list of ligands and receptors engaged by the PIE domain will grow as we come to better understand how this versatile structural architecture can be tailored to manipulate host responses to infection.

Origin and Evolution of Protein Fold Designs Inferred from Phylogenomic Analysis of CATH Domain Structures in Proteomes

Science.gov (United States)

Bukhari, Syed Abbas; Caetano-Anollés, Gustavo

2013-01-01

The spatial arrangements of secondary structures in proteins, irrespective of their connectivity, depict the overall shape and organization of protein domains. These features have been used in the CATH and SCOP classifications to hierarchically partition fold space and define the architectural make up of proteins. Here we use phylogenomic methods and a census of CATH structures in hundreds of genomes to study the origin and diversification of protein architectures (A) and their associated topologies (T) and superfamilies (H). Phylogenies that describe the evolution of domain structures and proteomes were reconstructed from the structural census and used to generate timelines of domain discovery. Phylogenies of CATH domains at T and H levels of structural abstraction and associated chronologies revealed patterns of reductive evolution, the early rise of Archaea, three epochs in the evolution of the protein world, and patterns of structural sharing between superkingdoms. Phylogenies of proteomes confirmed the early appearance of Archaea. While these findings are in agreement with previous phylogenomic studies based on the SCOP classification, phylogenies unveiled sharing patterns between Archaea and Eukarya that are recent and can explain the canonical bacterial rooting typically recovered from sequence analysis. Phylogenies of CATH domains at A level uncovered general patterns of architectural origin and diversification. The tree of A structures showed that ancient structural designs such as the 3-layer (αβα) sandwich (3.40) or the orthogonal bundle (1.10) are comparatively simpler in their makeup and are involved in basic cellular functions. In contrast, modern structural designs such as prisms, propellers, 2-solenoid, super-roll, clam, trefoil and box are not widely distributed and were probably adopted to perform specialized functions. Our timelines therefore uncover a universal tendency towards protein structural complexity that is remarkable. PMID:23555236

Magnetic field effect on Gd2(MoO4)3 domain structure formation in the phase transformation range

International Nuclear Information System (INIS)

Flerova, S.A.; Tsinman, I.L.

1987-01-01

The behaviour of ferroelastic-ferroelectric domain structure of gadolinium molybdate crystal (GMO)during its formation in the magnetic field in the vicinity of phase transformation is studied.It is shown that the formation of domain structure in the presence of a temperature gradient occurs in the field of mechanical stresses whose mainly stretching effect is concentrated near phase boundaries.The magnetic field intensifies summary mechanical stresses where a domain structure in a ferroelectric phase is formed due to interaction with the elements of inhomogeneous and differently oriented currents near phase boundaries

Ferroelectric domain structures in -oriented K0.15Na0.85NbO3 lead-free single crystal

Directory of Open Access Journals (Sweden)

Yan Chen

2015-03-01

Full Text Available In this work, ferroelectric domain structures of -oriented K0.15Na0.85NbO3 single crystal are characterized. Transmission electron microscopy (TEM observation revealed high-density of laminate domain structures in the crystal and the lattices of the neighboring domains are found to be twisted in a small angle. Superlattice diffraction spots of 1 2 { eeo } and 1 2 { ooe } in electron diffraction patterns are observed in the crystal, revealing the a+a+c− tilting of oxygen octahedral in the perovskite structure. The piezoresponse of domains and in-situ poling responses of K0.15Na0.85NbO3 crystal are observed by piezoresponse force microscopy (PFM, and the results assure its good ferroelectric properties.

Alternative splicing originates different domain structure organization of Lutzomyia longipalpis chitinases.

Science.gov (United States)

Ortigão-Farias, João Ramalho; Di-Blasi, Tatiana; Telleria, Erich Loza; Andorinho, Ana Carolina; Lemos-Silva, Thais; Ramalho-Ortigão, Marcelo; Tempone, Antônio Jorge; Traub-Csekö, Yara Maria

2018-02-01

BACKGROUND The insect chitinase gene family is composed by more than 10 paralogs, which can codify proteins with different domain structures. In Lutzomyia longipalpis, the main vector of visceral leishmaniasis in Brazil, a chitinase cDNA from adult female insects was previously characterized. The predicted protein contains one catalytic domain and one chitin-binding domain (CBD). The expression of this gene coincided with the end of blood digestion indicating a putative role in peritrophic matrix degradation. OBJECTIVES To determine the occurrence of alternative splicing in chitinases of L. longipalpis. METHODS We sequenced the LlChit1 gene from a genomic clone and the three spliced forms obtained by reverse transcription polymerase chain reaction (RT-PCR) using larvae cDNA. FINDINGS We showed that LlChit1 from L. longipalpis immature forms undergoes alternative splicing. The spliced form corresponding to the adult cDNA was named LlChit1A and the two larvae specific transcripts were named LlChit1B and LlChit1C. The B and C forms possess stop codons interrupting the translation of the CBD. The A form is present in adult females post blood meal, L4 larvae and pre-pupae, while the other two forms are present only in L4 larvae and disappear just before pupation. Two bands of the expected size were identified by Western blot only in L4 larvae. MAIN CONCLUSIONS We show for the first time alternative splicing generating chitinases with different domain structures increasing our understanding on the finely regulated digestion physiology and shedding light on a potential target for controlling L. longipalpis larval development.

Protein structure similarity from principle component correlation analysis

Directory of Open Access Journals (Sweden)

Chou James

2006-01-01

Full Text Available Abstract Background Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities. Results We measure structural similarity between proteins by correlating the principle components of their secondary structure interaction matrix. In our approach, the Principle Component Correlation (PCC analysis, a symmetric interaction matrix for a protein structure is constructed with relationship parameters between secondary elements that can take the form of distance, orientation, or other relevant structural invariants. When using a distance-based construction in the presence or absence of encoded N to C terminal sense, there are strong correlations between the principle components of interaction matrices of structurally or topologically similar proteins. Conclusion The PCC method is extensively tested for protein structures that belong to the same topological class but are significantly different by RMSD measure. The PCC analysis can also differentiate proteins having similar shapes but different topological arrangements. Additionally, we demonstrate that when using two independently defined interaction matrices, comparison of their maximum

Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

Science.gov (United States)

Filippakopoulos, Panagis; Kofler, Michael; Hantschel, Oliver; Gish, Gerald D; Grebien, Florian; Salah, Eidarus; Neudecker, Philipp; Kay, Lewis E; Turk, Benjamin E; Superti-Furga, Giulio; Pawson, Tony; Knapp, Stefan

2008-09-05

The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

Mapping domain structures in silks from insects and spiders related to protein assembly.

Science.gov (United States)

Bini, Elisabetta; Knight, David P; Kaplan, David L

2004-01-02

The exceptional solubility in vivo (20-30%, w/v) of the silk proteins of insects and spiders is dictated by both the need to produce solid fibres with a high packing fraction and the high mesogen concentration required for lyotropic liquid crystalline spinning. A further design requirement for silk proteins is a strong predominance of hydrophobic amino acid residues to provide for the hydrophobic interactions, water exclusion, and beta-crystallite formation required to produce strong insoluble threads. Thus, the domain structure of silk proteins needs to enable nanoscale phase separation to achieve high solubility of hydrophobic proteins in aqueous solutions. Additionally, silk proteins need to avoid premature precipitation as beta-sheets during storage and processing. Here we use mapping of domain types, sizes and distributions in silks to identify consistent design features that have evolved to meet these requirements. We show that silk proteins consist of conspicuously hydrophilic terminal domains flanking a very long central portion constructed from hydrophobic blocks separated by hydrophilic ones, discussing the domain structure in detail. The general rules of construction for silk proteins based on our observations should give a useful guide to the way in which Nature has solved the problem of processing hydrophobic proteins in water and how this can be copied industrially. Following these rules may also help in obtaining adequate expression, soluble products and controllable conformational switches in the production of genetically engineered or chemically synthesized silk analogues. Thus these insights have implications for structural biology and relevance to fundamental and applied questions in material science and engineering.

Structural considerations for functional anti-EGFR × anti-CD3 bispecific diabodies in light of domain order and binding affinity.

Science.gov (United States)

Asano, Ryutaro; Nagai, Keisuke; Makabe, Koki; Takahashi, Kento; Kumagai, Takashi; Kawaguchi, Hiroko; Ogata, Hiromi; Arai, Kyoko; Umetsu, Mitsuo; Kumagai, Izumi

2018-03-02

We previously reported a functional humanized bispecific diabody (bsDb) that targeted EGFR and CD3 (hEx3-Db) and enhancement of its cytotoxicity by rearranging the domain order in the V domain. Here, we further dissected the effect of domain order in bsDbs on their cross-linking ability and binding kinetics to elucidate general rules regarding the design of functional bsDbs. Using Ex3-Db as a model system, we first classified the four possible domain orders as anti-parallel (where both chimeric single-chain components are variable heavy domain (VH)-variable light domain (VL) or VL-VH order) and parallel types (both chimeric single-chain components are mixed with VH-VL and VL-VH order). Although anti-parallel Ex3-Dbs could cross-link the soluble target antigens, their cross-linking ability between soluble targets had no correlation with their growth inhibitory effects. In contrast, the binding affinity of one of the two constructs with a parallel-arrangement V domain was particularly low, and structural modeling supported this phenomenon. Similar results were observed with E2x3-Dbs, in which the V region of the anti-EGFR antibody clone in hEx3 was replaced with that of another anti-EGFR clone. Only anti-parallel types showed affinity-dependent cancer inhibitory effects in each molecule, and E2x3-LH (both components in VL-VH order) showed the most intense anti-tumor activity in vitro and in vivo . Our results showed that, in addition to rearranging the domain order of bsDbs, increasing their binding affinity may be an ideal strategy for enhancing the cytotoxicity of anti-parallel constructs and that E2x3-LH is particularly attractive as a candidate next-generation anti-cancer drug.

Crystal structures of the UBX domain of human UBXD7 and its complex with p97 ATPase.

Science.gov (United States)

Li, Zhi-Hui; Wang, Yong; Xu, Min; Jiang, Tao

2017-04-22

In humans, UBXD7 (also called UBXN7), an adaptor of p97 ATPase, can participate in the degradation of misfolded or damaged proteins in the p97-mediated ubiquitin proteasome system (UPS). UBXD7 binds to ubiquitinated substrates via its UBA domain and interacts with p97 N-terminal domain through its UBX domain to recruit p97 or the p97 core complex (p97/NPL4/UFD1). Here, we report the crystal structures of the UBX domain of UBXD7 (UBXD7 UBX ) at 2.0 Å resolution and its complex with p97 N-terminal domain (p97 NTD -UBXD7 UBX complex) at 2.4 Å resolution. A structural analysis and isothermal titration calorimetry results provide detailed molecular basis of interaction between UBXD7 UBX and p97 NTD . Moreover, structural superpositions suggest that dimerization of UBXD7 UBX via an intermolecular disulfide bond could interfere with the formation of the p97 NTD -UBXD7 UBX complex. Interestingly, UBXD7 may have a cooperative effect on p97 interaction with UFD1. Together, these results provide structural and biochemical insights into the interaction between p97 NTD and UBXD7 UBX . Copyright © 2017 Elsevier Inc. All rights reserved.

Crystal structure of Arabidopsis thaliana Dawdle forkhead-associated domain reveals a conserved phospho-threonine recognition cleft for dicer-like 1 binding.

Science.gov (United States)

Machida, Satoru; Yuan, Y Adam

2013-07-01

Dawdle (DDL) is a microRNA processing protein essential for the development of Arabidopsis. DDL contains a putative nuclear localization signal at its amino-terminus and forkhead-associated (FHA) domain at the carboxyl-terminus. Here, we report the crystal structure of the FHA domain of Arabidopsis Dawdle, determined by multiple-wavelength anomalous dispersion method at 1.7-Å resolution. DDL FHA structure displays a seven-stranded β-sandwich architecture that contains a unique structural motif comprising two long anti-parallel strands. Strikingly, crystal packing of the DDL FHA domain reveals that a glutamate residue from the symmetry-related DDL FHA domain, a structural mimic of the phospho-threonine, is specifically recognized by the structurally conserved phospho-threonine binding cleft. Consistently with the structural observations, co-immuno-precipitation experiments performed in Nicotiana benthamiana show that the DDL FHA domain co-immuno-precipitates with DCL1 fragments containing the predicted pThr+3(Ile/Val/Leu/Asp) motif. Taken together, we count the recognition of the target residue by the canonical binding cleft of the DDL FHA domain as the key molecular event to instate FHA domain-mediated protein-protein interaction in plant miRNA processing.

Signatures of Quantum Transport Through Two-Dimensional Structures With Correlated and Anti-Correlated Interfaces

OpenAIRE

Low, Tony; Ansari, Davood

2008-01-01

Electronic transport through a 2D deca-nanometer length channel with correlated and anti-correlated surfaces morphologies is studied using the Keldysh non-equilibrium Green function technique. Due to the pseudo-periodicity of these structures, the energy-resolved transmission possesses pseudo-bands and pseudo-gaps. Channels with correlated surfaces exhibit wider pseudo-bands than their anti-correlated counterparts. By surveying channels with various combinations of material parameters, we fou...

The study of co-citation analysis and knowledge structure on healthcare domain

Science.gov (United States)

Chu, Kuo-Chung; Liu, Wen-I.; Tsai, Ming-Yu

2012-11-01

With the prevalence of Internet and digital archives, the online e-journal database facilitates scholars to search literature in a research domain, or to cross-search an inter-disciplined field; the key literature can be efficiently traced out. This study intends to build a Web-based citation analysis system, which consists of four modules, they are: 1) literature search module; (2) statistics module; (3) articles analysis module; and (4) co-citation analysis module. The system focuses on PubMed Central dataset that has 170,000 records. In a research domain, a specific keyword searches in terms of authors, journals, and core issues. In addition, we use data mining techniques for co-citation analysis. The results assist researchers with in-depth understanding of the domain knowledge. Having an automated system for co-citation analysis, it helps to understand changes, trends, and knowledge structure of research domain. For the best of our knowledge, the proposed system differentiates from existing online electronic retrieval database analysis function. Perhaps, the proposed system is going to be a value-added database of healthcare domain, and hope to contribute the researchers.

The structure and dynamic properties of the complete histidine phosphotransfer domain of the chemotaxis specific histidine autokinase CheA from Thermotoga maritima

International Nuclear Information System (INIS)

Vu, Anh; Hamel, Damon J.; Zhou Hongjun; Dahlquist, Frederick W.

2011-01-01

The bacterial histidine autokinase CheA contains a histidine phosphotransfer (Hpt) domain that accepts a phosphate from the catalytic domain and donates the phosphate to either target response regulator protein, CheY or CheB. The Hpt domain forms a helix-bundle structure with a conserved four-helix bundle motif and a variable fifth helix. Observation of two nearly equally populated conformations in the crystal structure of a Hpt domain fragment of CheA from Thermotoga maritima containing only the first four helices suggests more mobility in a tightly packed helix bundle structure than previously thought. In order to examine how the structures of Hpt domain homologs may differ from each other particularly in the conformation of the last helix, and whether an alternative conformation exists in the intact Hpt domain in solution, we have solved a high-resolution, solution structure of the CheA Hpt from T. maritima and characterized the backbone dynamics of this protein. The structure contains a four-helix bundle characteristic of histidine phosphotransfer domains. The position and orientation of the fifth helix resembles those in known Hpt domain crystal and solution structures in other histidine kinases. The alternative conformation that was reported in the crystal structure of the CheA Hpt from T. maritima missing the fifth helix is not detected in the solution structure, suggesting a role for the fifth helix in providing stabilizing forces to the overall structure.

Neural Correlates of Expert Behavior During a Domain-Specific Attentional Cueing Task in Badminton Players.

Science.gov (United States)

Wang, Chun-Hao; Tu, Kuo-Cheng

2017-06-01

The present study aimed to investigate the neural correlates associated with sports expertise during a domain-specific task in badminton players. We compared event-related potentials activity from collegiate male badminton players and a set of matched athletic controls when they performed a badminton-specific attentional cueing task in which the uncertainty and validity were manipulated. The data showed that, regardless of cue type, the badminton players had faster responses along with greater P3 amplitudes than the athletic controls on the task. Specifically, the contingent negative variation amplitude was smaller for the players than for the controls in the condition involving higher uncertainty. Such an effect, however, was absent in the condition with lower uncertainty. We conclude that expertise in sports is associated with proficient modulation of brain activity during cognitive and motor preparation, as well as response execution, when performing a task related to an individual's specific sport domain.

Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein

Energy Technology Data Exchange (ETDEWEB)

Kellner, Julian N.; Meinhart, Anton, E-mail: anton.meinhart@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg (Germany)

2015-08-25

The structure of the SPRY domain of the human RNA helicase DDX1 was determined at 2.0 Å resolution. The SPRY domain provides a putative protein–protein interaction platform within DDX1 that differs from other SPRY domains in its structure and conserved regions. The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein–protein interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein–protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.

Hard-magnetic surface layer effect on the erbium orthoferrite plate domain structure in the region of gradual spin reorientation

International Nuclear Information System (INIS)

Belyaeva, A.I.; Vojtsenya, S.V.; Yur'ev, V.P.

1988-01-01

Rearrangement of domain structures in the erbium orthoferrite plates with hard-magnetic surface layer is investigated during gradual spin reorientation. This phenomenon is explained by means of the proposed physical models. It is shown that in these plates an approach to the temperature interval of spin reorientation causes a decrease in the density of energy of domain walls separating the internal and surface domains. This decrease results in transition to the domain structure which are close to equilibrium ones inside the crystal. 30 refs.; 4 figs

Electronic Structure of Strongly Correlated Materials

CERN Document Server

Anisimov, Vladimir

2010-01-01

Electronic structure and physical properties of strongly correlated materials containing elements with partially filled 3d, 4d, 4f and 5f electronic shells is analyzed by Dynamical Mean-Field Theory (DMFT). DMFT is the most universal and effective tool used for the theoretical investigation of electronic states with strong correlation effects. In the present book the basics of the method are given and its application to various material classes is shown. The book is aimed at a broad readership: theoretical physicists and experimentalists studying strongly correlated systems. It also serves as a handbook for students and all those who want to be acquainted with fast developing filed of condensed matter physics.

Magnetic domain structure investigation of Bi: YIG-thin films by combination of AFM and cantilever-based aperture SNOM

International Nuclear Information System (INIS)

Vysokikh, Yu E; Shevyakov, V I; Krasnoborodko, S Yu; Shelaev, A V; Prokopov, A R

2016-01-01

We present the results of magnetic domain structure investigation by combination of atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM). Special hollow-pyramid AFM cantilevers with aperture was used. This combination allows us use same probe for both topography and domain structure visualization of Bi -substituted ferrite garnet films of micro- and nano-meter thickness. Samples were excited through aperture by tightly focused linearly polarized laser beam. Magneto-optical effect rotates polarization of transmitted light depend on domain orientation. Visualization of magnetic domains was performed by detecting cross polarized component of transmitted light. SNOM allows to obtain high resolution magnetic domain image and prevent sample from any disturbance by magnetic probe. Same area SNOM and MFM images are presented. (paper)

Evolution of the RNase P RNA structural domain in Leptospira spp

NARCIS (Netherlands)

Ravishankar, Vigneshwaran; Ahmed, Ahmed; Sivagnanam, Ulaganathan; Muthuraman, Krishnaraja; Karthikaichamy, Anbarasu; Wilson, Herald A.; Devendran, Ajay; Hartskeerl, Rudy A.; Raj, Stephen M. L.

2014-01-01

We have employed the RNase P RNA (RPR) gene, which is present as single copy in chromosome I of Leptospira spp. to investigate the phylogeny of structural domains present in the RNA subunit of the tRNA processing enzyme, RNase P. RPR gene sequences of 150 strains derived from NCBI database along

Interplay between past market correlation structure changes and future volatility outbursts

Science.gov (United States)

Musmeci, Nicoló; Aste, Tomaso; Di Matteo, T.

2016-11-01

We report significant relations between past changes in the market correlation structure and future changes in the market volatility. This relation is made evident by using a measure of “correlation structure persistence” on correlation-based information filtering networks that quantifies the rate of change of the market dependence structure. We also measured changes in the correlation structure by means of a “metacorrelation” that measures a lagged correlation between correlation matrices computed over different time windows. Both methods show a deep interplay between past changes in correlation structure and future changes in volatility and we demonstrate they can anticipate market risk variations and this can be used to better forecast portfolio risk. Notably, these methods overcome the curse of dimensionality that limits the applicability of traditional econometric tools to portfolios made of a large number of assets. We report on forecasting performances and statistical significance of both methods for two different equity datasets. We also identify an optimal region of parameters in terms of True Positive and False Positive trade-off, through a ROC curve analysis. We find that this forecasting method is robust and it outperforms logistic regression predictors based on past volatility only. Moreover the temporal analysis indicates that methods based on correlation structural persistence are able to adapt to abrupt changes in the market, such as financial crises, more rapidly than methods based on past volatility.

Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies.

Science.gov (United States)

Bocharov, Eduard V; Lesovoy, Dmitry M; Goncharuk, Sergey A; Goncharuk, Marina V; Hristova, Kalina; Arseniev, Alexander S

2013-11-05

Fibroblast growth factor receptor 3 (FGFR3) transduces biochemical signals via lateral dimerization in the plasma membrane, and plays an important role in human development and disease. Eight different pathogenic mutations, implicated in cancers and growth disorders, have been identified in the FGFR3 transmembrane segment. Here, we describe the dimerization of the FGFR3 transmembrane domain in membrane-mimicking DPC/SDS (9/1) micelles. In the solved NMR structure, the two transmembrane helices pack into a symmetric left-handed dimer, with intermolecular stacking interactions occurring in the dimer central region. Some pathogenic mutations fall within the helix-helix interface, whereas others are located within a putative alternative interface. This implies that although the observed dimer structure is important for FGFR3 signaling, the mechanism of FGFR3-mediated transduction across the membrane is complex. We propose an FGFR3 signaling mechanism that is based on the solved structure, available structures of isolated soluble FGFR domains, and published biochemical and biophysical data. Copyright © 2013 Elsevier Ltd. All rights reserved.

Specific features of the domain structure of (Gd1-xNdx)2(MoO4)3 crystals

International Nuclear Information System (INIS)

Bryzgalov, A.N.; Slepchenko, B.M.; Virachev, B.P.

1989-01-01

Formation of the domain structures by sample transfer into thermodynamically metastable state using a simultaneous effect of electric field and temperature change is investigated in Gd 1.7 Nd 0.3 (MoO 4 ) 3 monocrystals (GMO). Some new results obtained under investigations into GMO domain structure using neodymium by means of hydrothermal etching and polarization-optical method are presented

Observation of the domain structure in Fe-Au superlattices with perpendicular anisotropy

Energy Technology Data Exchange (ETDEWEB)

Zoladz, M. E-mail: zoladz@uci.agh.edu.pl; Slezak, T.; Wilgocka-Slezak, D.; Spiridis, N.; Korecki, J.; Stobiecki, T. E-mail: stobieck@uci.agh.edu.pl; Roell, K

2004-05-01

Polar Kerr Microscopy was used to visualize characteristic transitions and external magnetic field driven domain structure evolution in a perpendicularly magnetized Fe-Au AF/FM double multilayer structure. Real time imaging performed in the external magnetic field allowed for identification of all sublayers magnetization reversal in accordance with measured PMOKE magnetization curve, showing strong dependence of transition character on the interlayer coupling type and adjacent sublayers magnetization orientation.

Observation of the domain structure in Fe-Au superlattices with perpendicular anisotropy

International Nuclear Information System (INIS)

Zoladz, M.; Slezak, T.; Wilgocka-Slezak, D.; Spiridis, N.; Korecki, J.; Stobiecki, T.; Roell, K.

2004-01-01

Polar Kerr Microscopy was used to visualize characteristic transitions and external magnetic field driven domain structure evolution in a perpendicularly magnetized Fe-Au AF/FM double multilayer structure. Real time imaging performed in the external magnetic field allowed for identification of all sublayers magnetization reversal in accordance with measured PMOKE magnetization curve, showing strong dependence of transition character on the interlayer coupling type and adjacent sublayers magnetization orientation

Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

KAUST Repository

Liang, Yu

2012-06-26

Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

KAUST Repository

Liang, Yu; Huimei Hong, Felicia; Ganesan, Pugalenthi; Jiang, Sizun; Jauch, Ralf; Stanton, Lawrence W.; Kolatkar, Prasanna R.

2012-01-01

Zfp206 (also named as Zscan10) belongs to the subfamily of C2H2 zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C2H2 transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development. 2012 The Author(s).

Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein

International Nuclear Information System (INIS)

Delorme, Caroline; Joshi, Monika; Allingham, John S.

2012-01-01

Highlights: ► The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. ► The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. ► The MBP–Kar3 interface highlights a new site for intramolecular or intermolecular interactions. -- Abstract: In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3 (CaKar3) is critical for normal mitotic division, nuclear fusion during mating, and morphogenic transition from the commensal yeast form to the virulent hyphal form. As a first step towards detailed characterization of this motor of potential medical significance, we have crystallized and determined the X-ray structure of the motor domain of CaKar3 as a maltose-binding protein (MBP) fusion. The structure shows strong conservation of overall motor domain topology to other Kar3 kinesins, but with some prominent differences in one of the motifs that compose the nucleotide-binding pocket and the surface charge distribution. The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor domain core at the same site where the neck linker of conventional kinesins docks during the “ATP state” of the mechanochemical cycle. This site differs from the Kar3 neck–core interface in the recent structure of the ScKar3Vik1 heterodimer. The position of MBP is also completely distinct from the Vik1 subunit in this complex. This may suggest that the site of MBP interaction on the CaKar3 motor domain provides an interface for the neck, or perhaps a partner subunit, at an intermediate state of its motile cycle that has not yet been observed for Kinesin-14 motors.

Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein

Energy Technology Data Exchange (ETDEWEB)

Delorme, Caroline; Joshi, Monika [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada); Allingham, John S., E-mail: allinghj@queensu.ca [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada)

2012-11-30

Highlights: Black-Right-Pointing-Pointer The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. Black-Right-Pointing-Pointer The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. Black-Right-Pointing-Pointer The MBP-Kar3 interface highlights a new site for intramolecular or intermolecular interactions. -- Abstract: In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3 (CaKar3) is critical for normal mitotic division, nuclear fusion during mating, and morphogenic transition from the commensal yeast form to the virulent hyphal form. As a first step towards detailed characterization of this motor of potential medical significance, we have crystallized and determined the X-ray structure of the motor domain of CaKar3 as a maltose-binding protein (MBP) fusion. The structure shows strong conservation of overall motor domain topology to other Kar3 kinesins, but with some prominent differences in one of the motifs that compose the nucleotide-binding pocket and the surface charge distribution. The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor domain core at the same site where the neck linker of conventional kinesins docks during the 'ATP state' of the mechanochemical cycle. This site differs from the Kar3 neck-core interface in the recent structure of the ScKar3Vik1 heterodimer. The position of MBP is also completely distinct from the Vik1 subunit in this complex. This may suggest that the site of MBP interaction on the CaKar3 motor domain provides an interface for the neck, or perhaps a partner subunit, at an intermediate state of its motile cycle that has not yet been observed for Kinesin-14 motors.

The secondary structure of large-subunit rRNA divergent domains, a marker for protist evolution

DEFF Research Database (Denmark)

Lenaers, G; Nielsen, Henrik; Engberg, J

1988-01-01

The secondary structure of the large-subunit ribosomal RNA (24-26S rRNA) has been studied with emphasis on comparative analysis of the folding patterns of the divergent domains in the available protist sequences, that is Prorocentrum micans (dinoflagellate), Saccharomyces carlsbergensis (yeast......), Tetrahymena thermophila (ciliate), Physarum polycephalum and Dictyostelium discoideum (slime moulds), Crithidia fasciculata and Giardia lamblia (parasitic flagellates). The folding for the D3, D7a and D10 divergent domains has been refined and a consensus model for the protist 24-26S rRNA structure...

Micro-structure-mobility correlation in self-organised, conjugated polymer field-effect transistors

NARCIS (Netherlands)

Sirringhaus, H.; Brown, P.J.; Friend, R.H.; Nielsen, M.M.; Bechgaard, K.; Langeveld-Voss, B.M.W.; Spiering, A.J.H.; Janssen, R.A.J.; Meijer, E.W.

2000-01-01

We have investigated the correlation between polymer microstructure and charge carrier mobility in high-mobility, self-organised field-effect transistors of poly-3-hexyl-thiophene (P3HT). Two different preferential orientations of the microcrystalline P3HT domains with respect to the substrate have

Influence of thermal light correlations on photosynthetic structures

Science.gov (United States)

de Mendoza, Adriana; Manrique, Pedro; Caycedo-Soler, Felipe; Johnson, Neil F.; Rodríguez, Ferney J.; Quiroga, Luis

2014-03-01

The thermal light from the sun is characterized by both classical and quantum mechanical correlations. These correlations have left a fingerprint on the natural harvesting structures developed through five billion years of evolutionary pressure, specially in photosynthetic organisms. In this work, based upon previous extensive studies of spatio-temporal correlations of light fields, we hypothesize that structures involving photosensitive pigments like those present in purple bacteria vesicles emerge as an evolutionary response to the different properties of incident light. By using burstiness and memory as measures that quantify higher moments of the photon arrival statistics, we generate photon-time traces. They are used to simulate absorption on detectors spatially extended over regions comparable to these light fields coherence length. Finally, we provide some insights into the connection between these photo-statistical features with the photosynthetic membrane architecture and the lights' spatial correlation. Facultad de Ciencias Uniandes.

Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

Science.gov (United States)

Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto

2016-03-27

In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. Copyright © 2016 Elsevier Ltd. All rights reserved.

Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain

DEFF Research Database (Denmark)

Sükösd, Zsuzsanna; Andersen, Ebbe Sloth; Seemann, Ernst Stefan

2015-01-01

of the HIV-1 genome is highly variable in most regions, with a limited number of stable and conserved RNA secondary structures. Most interesting, a set of long distance interactions form a core organizing structure (COS) that organize the genome into three major structural domains. Despite overlapping...

Analysis of the Sequences, Structures, and Functions of Product-Releasing Enzyme Domains in Fungal Polyketide Synthases

Directory of Open Access Journals (Sweden)

Lu Liu

2017-09-01

Full Text Available Product-releasing enzyme (PRE domains in fungal non-reducing polyketide synthases (NR-PKSs play a crucial role in catalysis and editing during polyketide biosynthesis, especially accelerating final biosynthetic reactions accompanied with product offloading. However, up to date, the systematic knowledge about PRE domains is deficient. In the present study, the relationships between sequences, structures, and functions of PRE domains were analyzed with 574 NR-PKSs of eight groups (I–VIII. It was found that the PRE domains in NR-PKSs could be mainly classified into three types, thioesterase (TE, reductase (R, and metallo-β-lactamase-type TE (MβL-TE. The widely distributed TE or TE-like domains were involved in NR-PKSs of groups I–IV, VI, and VIII. The R domains appeared in NR-PKSs of groups IV and VII, while the physically discrete MβL-TE domains were employed by most NR-PKSs of group V. The changes of catalytic sites and structural characteristics resulted in PRE functional differentiations. The phylogeny revealed that the evolution of TE domains was accompanied by complex functional divergence. The diverse sequence lengths of TE lid-loops affected substrate specificity with different chain lengths. The volume diversification of TE catalytic pockets contributed to catalytic mechanisms with functional differentiations. The above findings may help to understand the crucial catalysis of fungal aromatic polyketide biosyntheses and govern recombination of NR-PKSs to obtain unnatural target products.

Structures of Staphylococcus aureus D-tagatose-6-phosphate kinase implicate domain motions in specificity and mechanism.

Science.gov (United States)

Miallau, Linda; Hunter, William N; McSweeney, Sean M; Leonard, Gordon A

2007-07-06

High resolution structures of Staphylococcus aureus d-tagatose-6-phosphate kinase (LacC) in two crystal forms are herein reported. The structures define LacC in apoform, in binary complexes with ADP or the co-factor analogue AMP-PNP, and in a ternary complex with AMP-PNP and D-tagatose-6-phosphate. The tertiary structure of the LacC monomer, which is closely related to other members of the pfkB subfamily of carbohydrate kinases, is composed of a large alpha/beta core domain and a smaller, largely beta "lid." Four extended polypeptide segments connect these two domains. Dimerization of LacC occurs via interactions between lid domains, which come together to form a beta-clasp structure. Residues from both subunits contribute to substrate binding. LacC adopts a closed structure required for phosphoryl transfer only when both substrate and co-factor are bound. A reaction mechanism similar to that used by other phosphoryl transferases is proposed, although unusually, when both substrate and co-factor are bound to the enzyme two Mg(2+) ions are observed in the active site. A new motif of amino acid sequence conservation common to the pfkB subfamily of carbohydrate kinases is identified.

Structural brain correlates associated with professional handball playing.

Science.gov (United States)

Hänggi, Jürgen; Langer, Nicolas; Lutz, Kai; Birrer, Karin; Mérillat, Susan; Jäncke, Lutz

2015-01-01

There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands. We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM) of the primary/secondary motor (MI/supplementary motor area, SMA) and somatosensory cortex (SI/SII), basal ganglia, thalamus, and cerebellum and in the white matter (WM) of the corticospinal tract (CST) and corpus callosum, stronger in brain regions controlling the non-dominant left hand. Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA) and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women. Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic adaptations rather than a genetic predisposition for a ball playing

Structural brain correlates associated with professional handball playing.

Directory of Open Access Journals (Sweden)

Jürgen Hänggi

Full Text Available There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands.We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM of the primary/secondary motor (MI/supplementary motor area, SMA and somatosensory cortex (SI/SII, basal ganglia, thalamus, and cerebellum and in the white matter (WM of the corticospinal tract (CST and corpus callosum, stronger in brain regions controlling the non-dominant left hand.Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women.Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic adaptations rather than a genetic predisposition for a

Structural Brain Correlates Associated with Professional Handball Playing

Science.gov (United States)

Hänggi, Jürgen; Langer, Nicolas; Lutz, Kai; Birrer, Karin; Mérillat, Susan; Jäncke, Lutz

2015-01-01

Background There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands. Methodology/Hypotheses We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM) of the primary/secondary motor (MI/supplementary motor area, SMA) and somatosensory cortex (SI/SII), basal ganglia, thalamus, and cerebellum and in the white matter (WM) of the corticospinal tract (CST) and corpus callosum, stronger in brain regions controlling the non-dominant left hand. Results Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA) and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women. Discussion/Conclusion Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic

Structure-based design of ligands for protein basic domains: Application to the HIV-1 Tat protein

Science.gov (United States)

Filikov, Anton V.; James, Thomas L.

1998-05-01

A methodology has been developed for designing ligands to bind a flexible basic protein domain where the structure of the domain is essentially known. It is based on an empirical binding free energy function developed for highly charged complexes and on Monte Carlo simulations in internal coordinates with both the ligand and the receptor being flexible. HIV-1 encodes a transactivating regulatory protein called Tat. Binding of the basic domain of Tat to TAR RNA is required for efficient transcription of the viral genome. The structure of a biologically active peptide containing the Tat basic RNA-binding domain is available from NMR studies. The goal of the current project is to design a ligand which will bind to that basic domain and potentially inhibit the TAR-Tat interaction. The basic domain contains six arginine and two lysine residues. Our strategy was to design a ligand for arginine first and then a superligand for the basic domain by joining arginine ligands with a linker. Several possible arginine ligands were obtained by searching the Available Chemicals Directory with DOCK 3.5 software. Phytic acid, which can potentially bind multiple arginines, was chosen as a building block for the superligand. Calorimetric binding studies of several compounds to methylguanidine and Arg-/Lys-containing peptides were performed. The data were used to develop an empirical binding free energy function for prediction of affinity of the ligands for the Tat basic domain. Modeling of the conformations of the complexes with both the superligand and the basic domain being flexible has been carried out via Biased Probability Monte Carlo (BPMC) simulations in internal coordinates (ICM 2.6 suite of programs). The simulations used parameters to ensure correct folding, i.e., consistent with the experimental NMR structure of a 25-residue Tat peptide, from a random starting conformation. Superligands for the basic domain were designed by joining together two molecules of phytic acid with

Molecular dynamics simulations revealed structural differences among WRKY domain-DNA interaction in barley (Hordeum vulgare).

Science.gov (United States)

Pandey, Bharati; Grover, Abhinav; Sharma, Pradeep

2018-02-12

The WRKY transcription factors are a class of DNA-binding proteins involved in diverse plant processes play critical roles in response to abiotic and biotic stresses. Genome-wide divergence analysis of WRKY gene family in Hordeum vulgare provided a framework for molecular evolution and functional roles. So far, the crystal structure of WRKY from barley has not been resolved; moreover, knowledge of the three-dimensional structure of WRKY domain is pre-requisites for exploring the protein-DNA recognition mechanisms. Homology modelling based approach was used to generate structures for WRKY DNA binding domain (DBD) and its variants using AtWRKY1 as a template. Finally, the stability and conformational changes of the generated model in unbound and bound form was examined through atomistic molecular dynamics (MD) simulations for 100 ns time period. In this study, we investigated the comparative binding pattern of WRKY domain and its variants with W-box cis-regulatory element using molecular docking and dynamics (MD) simulations assays. The atomic insight into WRKY domain exhibited significant variation in the intermolecular hydrogen bonding pattern, leading to the structural anomalies in the variant type and differences in the DNA-binding specificities. Based on the MD analysis, residual contribution and interaction contour, wild-type WRKY (HvWRKY46) were found to interact with DNA through highly conserved heptapeptide in the pre- and post-MD simulated complexes, whereas heptapeptide interaction with DNA was missing in variants (I and II) in post-MD complexes. Consequently, through principal component analysis, wild-type WRKY was also found to be more stable by obscuring a reduced conformational space than the variant I (HvWRKY34). Lastly, high binding free energy for wild-type and variant II allowed us to conclude that wild-type WRKY-DNA complex was more stable relative to variants I. The results of our study revealed complete dynamic and structural information

A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

Science.gov (United States)

Li-Smerin, Y; Hackos, D H; Swartz, K J

2000-02-01

Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.

Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy.

OpenAIRE

Markl, Daniel; Bawuah, Prince; Ridgway, Cathy; van den Ban, Sander; Goodwin, Daniel J; Ketolainen, Jarkko; Gane, Patrick; Peiponen, Kai-Erik; Zeitler, Jochen Axel

2018-01-01

Pharmaceutical tablets are typically manufactured by the uni-axial compaction of powder that is confined radially by a rigid die. The directional nature of the compaction process yields not only anisotropic mechanical properties (e.g. tensile strength) but also directional properties of the pore structure in the porous compact. This study derives a new quantitative parameter, $S_a$, to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectrosc...

Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

Science.gov (United States)

Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

2018-01-01

The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

EH domain of EHD1

Energy Technology Data Exchange (ETDEWEB)

Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve, E-mail: scaplan@unmc.edu; Sorgen, Paul L. [University of Nebraska Medical Center, Department of Biochemistry and Molecular Biology and Eppley Cancer Center (United States)], E-mail: psorgen@unmc.edu

2007-12-15

EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed.

EH domain of EHD1

International Nuclear Information System (INIS)

Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

2007-01-01

EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed

The four-domain structure model of a depression scale for medical students: A cross-sectional study in Haiphong, Vietnam.

Science.gov (United States)

Nguyen, Thao Thi Thu; Nguyen, Ngoc Thi Minh; Pham, Manh Van; Pham, Han Van; Nakamura, Hiroyuki

2018-01-01

Depression is a common mental health problem with a higher prevalence in medical students than in the general population. This study aims to investigate the association between depressive symptoms, particularly those in each domain of the Center for Epidemiological Studies Depression (CES-D) Scale, and related factors. A cross-sectional study was conducted with a random sample of 1319 medical students at Haiphong University of Medicine and Pharmacy in 2016. The CES-D scale and a self-reported questionnaire were used to identify the prevalence of depressive symptoms and related risk factors. Univariate and multivariate logistic regression were performed to assess the risk factors associated with depressive symptoms and the score for each structure factor. Depressive symptoms were observed in 514 (39%) students, including more males than females (44.2% vs 36.9%, p = 0.015). Students whose mothers' highest education level was primary school had a higher prevalence of depressive symptoms than students whose mothers had higher education levels (p = 0.038). There was a significant relationship between depressive symptoms and stressful life events, especially a decline in personal health. A higher correlation was found between the somatic complaints and depressive affect domains. The impacts of risk factors differed for each domain of the depression scale. Only the factor of achieving excellence showed no statistically significant associations with depressive symptoms and the scores on the four domains considered in this study. The high prevalence of depressive symptoms among medical students with risk factors and the impact of these risk factors on each domain of depression scale need further clarification to alleviate depression in students during their medical training.

The diagnostic use of choroidal thickness analysis and its correlation with visual field indices in glaucoma using spectral domain optical coherence tomography.

Directory of Open Access Journals (Sweden)

Zhongjing Lin

Full Text Available To evaluate the quantitative characteristics of choroidal thickness in primary open-angle glaucoma (POAG, normal tension glaucoma (NTG and in normal eyes using spectral-domain optical coherence tomography (SD-OCT. To evaluate the diagnostic ability of choroidal thickness in glaucoma and to determine the correlation between choroidal thickness and visual field parameters in glaucoma.A total of 116 subjects including 40 POAG, 30 NTG and 46 healthy subjects were enrolled in this study. Choroidal thickness measurements were acquired in the macular and peripapillary regions using SD-OCT. All subjects underwent white-on-white (W/W and blue-on-yellow (B/Y visual field tests using Humphrey Field Analyzer. The receiver operating characteristic (ROC curve and the area under curve (AUC were generated to assess the discriminating power of choroidal thickness for glaucoma. Pearson's correlation coefficients were calculated to assess the structure function correlation for glaucoma patients.No significant differences were observed for macular choroidal thickness among the different groups (all P > 0.05. Regarding the peripapillary choroidal thickness (PPCT, significant differences were observed among the three groups (all P 0.05, but showed significant correlations with B/Y MD (all P < 0.05. In the early glaucomatous eyes, PPCT showed significant correlations with W/W MD and B/Y MD (all P < 0.05.In our study, peripapillary choroidal thickness measured on OCT showed a low to moderate but statistically significant diagnostic power and a significant correlation with blue-on-yellow visual field indices in glaucoma. This may indicate a potential adjunct for peripapillary choroidal thickness in glaucoma diagnosis.

Fast conformational exchange between the sulfur-free and persulfide-bound rhodanese domain of E. coli YgaP

Energy Technology Data Exchange (ETDEWEB)

Wang, Wei [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhou, Peng [High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); He, Yao; Yu, Lu; Xiong, Ying [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Tian, Changlin, E-mail: cltian@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Wu, Fangming, E-mail: fmwu@hmfl.ac.cn [High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China)

2014-09-26

Highlights: • Three dimensional solution NMR structure of YgaP rhodanese domain. • Function validation of YgaP rhodanese domain to substrate Na{sub 2}S{sub 2}O{sub 3}. • Fast exchange between the intact and persulfide-intermediate rhodanese domain. - Abstract: Rhodanese domains are abundant structural modules that catalyze the transfer of a sulfur atom from thiolsulfates to cyanide via formation of a covalent persulfide intermediate that is bound to an essential conserved cysteine residue. In this study, the three-dimensional structure of the rhodanese domain of YgaP from Escherichia coli was determined using solution NMR. A typical rhodanese domain fold was observed, as expected from the high homology with the catalytic domain of other sulfur transferases. The initial sulfur-transfer step and formation of the rhodanese persulfide intermediate were monitored by addition of sodium thiosulfate using two-dimensional {sup 1}H–{sup 15}N correlation spectroscopy. Discrete sharp signals were observed upon substrate addition, indicting fast exchange between sulfur-free and persulfide-intermediate forms. Residues exhibiting pronounced chemical shift changes were mapped to the structure, and included both substrate binding and surrounding residues.

Characterization of radon penetration of different structural domains of concrete. Final project report

International Nuclear Information System (INIS)

Nielson, K.K.; Rogers, V.C.

1996-05-01

This report documents the research activities by Rogers and Associates Engineering Corporation on grant DE-FG03-93ER61600 during the funded project period from August 1993 to April 1996. The objective of this research was to characterize the mechanisms and rates of radon gas penetration of the different structural domains of the concrete components of residential floor slabs, walls, and associated joints and penetrations. The research was also to characterize the physical properties of the concretes in these domains to relate their radon resistance to their physical properties. These objectives support the broader goal of characterizing which, if any, concrete domains and associated properties constitute robust barriers to radon and which permit radon entry, either inherently or in ways that could be remediated or avoided

Structural modeling of the N-terminal signal–receiving domain of IκBα

Directory of Open Access Journals (Sweden)

Samira eYazdi

2015-06-01

Full Text Available The transcription factor nuclear factor-κB (NF-κB exerts essential roles in many biological processes including cell growth, apoptosis and innate and adaptive immunity. The NF-kB inhibitor (IκBα retains NF-κB in the cytoplasm and thus inhibits nuclear localization of NF-κB and its association with DNA. Recent protein crystal structures of the C-terminal part of IκBα in complex with NF-κB provided insights into the protein-protein interactions but could not reveal structural details about the N-terminal signal receiving domain (SRD. The SRD of IκBα contains a degron, formed following phosphorylation by IκB kinases (IKK. In current protein X-ray structures, however, the SRD is not resolved and assumed to be disordered. Here, we combined secondary structure annotation and domain threading followed by long molecular dynamics (MD simulations and showed that the SRD possesses well-defined secondary structure elements. We show that the SRD contains 3 additional stable α-helices supplementing the six ARDs present in crystallized IκBα. The IκBα/NF-κB protein-protein complex remained intact and stable during the entire simulations. Also in solution, free IκBα retains its structural integrity. Differences in structural topology and dynamics were observed by comparing the structures of NF-κB free and NF-κB bound IκBα-complex. This study paves the way for investigating the signaling properties of the SRD in the IκBα degron. A detailed atomic scale understanding of molecular mechanism of NF-κB activation, regulation and the protein-protein interactions may assist to design and develop novel chronic inflammation modulators.

Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA).

Science.gov (United States)

Wang, Li Kai; Zhu, Hui; Shuman, Stewart

2009-03-27

NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria, where they are essential for growth and present attractive targets for antimicrobial drug discovery. LigA has a distinctive modular structure in which a nucleotidyltransferase catalytic domain is flanked by an upstream NMN-binding module and by downstream OB-fold, zinc finger, helix-hairpin-helix, and BRCT domains. Here we conducted a structure-function analysis of the nucleotidyltransferase domain of Escherichia coli LigA, guided by the crystal structure of the LigA-DNA-adenylate intermediate. We tested the effects of 29 alanine and conservative mutations at 15 amino acids on ligase activity in vitro and in vivo. We thereby identified essential functional groups that coordinate the reactive phosphates (Arg(136)), contact the AMP adenine (Lys(290)), engage the phosphodiester backbone flanking the nick (Arg(218), Arg(308), Arg(97) plus Arg(101)), or stabilize the active domain fold (Arg(171)). Finer analysis of the mutational effects revealed step-specific functions for Arg(136), which is essential for the reaction of LigA with NAD(+) to form the covalent ligase-AMP intermediate (step 1) and for the transfer of AMP to the nick 5'-PO(4) to form the DNA-adenylate intermediate (step 2) but is dispensable for phosphodiester formation at a preadenylylated nick (step 3).

High resolution coherence domain depth-resolved nailfold capillaroscopy based on correlation mapping optical coherence tomography

Science.gov (United States)

Subhash, Hrebesh M.; O'Gorman, Sean; Neuhaus, Kai; Leahy, Martin

2014-03-01

In this paper we demonstrate a novel application of correlation mapping optical coherence tomography (cm-OCT) for volumetric nailfold capillaroscopy (NFC). NFC is a widely used non-invasive diagnostic method to analyze capillary morphology and microvascular abnormalities of nailfold area for a range of disease conditions. However, the conventional NFC is incapable of providing volumetric imaging, when volumetric quantitative microangiopathic parameters such as plexus morphology, capillary density, and morphologic anomalies of the end row loops most critical. cm-OCT is a recently developed well established coherence domain magnitude based angiographic modality, which takes advantage of the time-varying speckle effect, which is normally dominant in the vicinity of vascular regions compared to static tissue region. It utilizes the correlation coefficient as a direct measurement of decorrelation between two adjacent B-frames to enhance the visibility of depth-resolved microcirculation.

Identifying the structure of group correlation in the Korean financial market

Science.gov (United States)

Ahn, Sanghyun; Choi, Jaewon; Lim, Gyuchang; Cha, Kil Young; Kim, Sooyong; Kim, Kyungsik

2011-06-01

We investigate the structure of the cross-correlation in the Korean stock market. We analyze daily cross-correlations between price fluctuations of 586 different Korean stock entities for the 6-year time period from 2003 to 2008. The main purpose is to investigate the structure of group correlation and its stability by undressing the market-wide effect using the Markowitz multi-factor model and the network-based approach. We find the explicit list of significant firms in the few largest eigenvectors from the undressed correlation matrix. We also observe that each contributor is involved in the same business sectors. The structure of group correlation can not remain constant during each 1-year time period with different starting points, whereas only two largest eigenvectors are stable for 6 years 8-9 eigenvectors remain stable for half-year. The structure of group correlation in the Korean financial market is disturbed during a sufficiently short time period even though the group correlation exists as an ensemble for the 6-year time period in the evolution of the system. We verify the structure of group correlation by applying a network-based approach. In addition, we examine relations between market capitalization and businesses. The Korean stock market shows a different behavior compared to mature markets, implying that the KOSPI is a target for short-positioned investors.

Simulations of super-structure domain walls in two dimensional assemblies of magnetic nanoparticles

International Nuclear Information System (INIS)

Jordanovic, J.; Frandsen, C.; Beleggia, M.; Schiøtz, J.

2015-01-01

We simulate the formation of domain walls in two-dimensional assemblies of magnetic nanoparticles. Particle parameters are chosen to match recent electron holography and Lorentz microscopy studies of almost monodisperse cobalt nanoparticles assembled into regular, elongated lattices. As the particles are small enough to consist of a single magnetic domain each, their magnetic interactions can be described by a spin model in which each particle is assigned a macroscopic “superspin.” Thus, the magnetic behaviour of these lattices may be compared to magnetic crystals with nanoparticle superspins taking the role of the atomic spins. The coupling is, however, different. The superspins interact only by dipolar interactions as exchange coupling between individual nanoparticles may be neglected due to interparticle spacing. We observe that it is energetically favorable to introduce domain walls oriented along the long dimension of nanoparticle assemblies rather than along the short dimension. This is unlike what is typically observed in continuous magnetic materials, where the exchange interaction introduces an energetic cost proportional to the area of the domain walls. Structural disorder, which will always be present in realistic assemblies, pins longitudinal domain walls when the external field is reversed, and makes a gradual reversal of the magnetization by migration of longitudinal domain walls possible, in agreement with previous experimental results

Crystal structure of the extracellular domain of human myelin protein zero

Energy Technology Data Exchange (ETDEWEB)

Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C. (WSU-MED); (NWU)

2012-03-27

Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125

Static and high-frequency magnetic properties of stripe domain structure in a plate of finite sizes

International Nuclear Information System (INIS)

Mal'ginova, S.D.; Doroshenko, R.A.; Shul'ga, N.V.

2006-01-01

A model that enables to carry out self-consistent calculations of the main parameters of stripe domain structure (DS) and at the same time those of properties of domain walls (DW) of a multiple-axis finite (in all directions) ferromagnet depending on the sizes of a sample, material parameters and intensity of a magnetic field is offered. The calculations of the properties of DS (direction of magnetization in domains, widths, ferromagnetic resonance, etc.) are carried out on a computer for plates (1 1 0), rectangular shapes of a cubic ferromagnet with axes of light magnetization along trigonal directions in a magnetic field [-1 1 0]. It is shown, that in plates of different shapes there can be a structure with Neel DW alongside with DS with Bloch DW. Their features are noticeably exhibited, in particular, in different dependence of the number of domains, and also frequencies of a ferromagnetic resonance from a magnetic field

Simulations of super-structure domain walls in two dimensional assemblies of magnetic nanoparticles

DEFF Research Database (Denmark)

Jordanovic, Jelena; Beleggia, Marco; Schiøtz, Jakob

2015-01-01

We simulate the formation of domain walls in two-dimensional assemblies of magnetic nanoparticles. Particle parameters are chosen to match recent electron holography and Lorentz microscopy studies of almost monodisperse cobalt nanoparticles assembled into regular, elongated lattices. As the parti......We simulate the formation of domain walls in two-dimensional assemblies of magnetic nanoparticles. Particle parameters are chosen to match recent electron holography and Lorentz microscopy studies of almost monodisperse cobalt nanoparticles assembled into regular, elongated lattices...... taking the role of the atomic spins. The coupling is, however, different. The superspins interact only by dipolar interactions as exchange coupling between individual nanoparticles may be neglected due to interparticle spacing. We observe that it is energetically favorable to introduce domain walls...... oriented along the long dimension of nanoparticle assemblies rather than along the short dimension. This is unlike what is typically observed in continuous magnetic materials, where the exchange interaction introduces an energetic cost proportional to the area of the domain walls. Structural disorder...

Structure of the Reston ebolavirus VP30 C-terminal domain.

Science.gov (United States)

Clifton, Matthew C; Kirchdoerfer, Robert N; Atkins, Kateri; Abendroth, Jan; Raymond, Amy; Grice, Rena; Barnes, Steve; Moen, Spencer; Lorimer, Don; Edwards, Thomas E; Myler, Peter J; Saphire, Erica Ollmann

2014-04-01

The ebolaviruses can cause severe hemorrhagic fever. Essential to the ebolavirus life cycle is the protein VP30, which serves as a transcriptional cofactor. Here, the crystal structure of the C-terminal, NP-binding domain of VP30 from Reston ebolavirus is presented. Reston VP30 and Ebola VP30 both form homodimers, but the dimeric interfaces are rotated relative to each other, suggesting subtle inherent differences or flexibility in the dimeric interface.

Structure and function of the TIR domain from the grape NLR protein RPV1

Directory of Open Access Journals (Sweden)

Simon John Williams

2016-12-01

Full Text Available The N-terminal Toll/interleukin-1 receptor/resistance protein (TIR domain has been shown to be both necessary and sufficient for defence signalling in the model plants flax and Arabidopsis. In examples from these organisms, TIR domain self-association is required for signalling function, albeit through distinct interfaces. Here, we investigate these properties in the TIR domain containing resistance protein RPV1 from the wild grapevine Muscadinia rotundifolia. The RPV1 TIR domain, without additional flanking sequence present, is autoactive when transiently expressed in tobacco, demonstrating that the TIR domain alone is capable of cell-death signalling. We determined the crystal structure of the RPV1 TIR domain at 2.3 Å resolution. In the crystals, the RPV1 TIR domain forms a dimer, mediated predominantly through residues in the αA and αE helices (AE interface. This interface is shared with the interface discovered in the dimeric complex of the TIR domains from the Arabidopsis RPS4/RRS1 resistance protein pair. We show that surface-exposed residues in the AE interface that mediate the dimer interaction in the crystals are highly conserved among plant TIR domain-containing proteins. While we were unable to demonstrate self-association of the RPV1 TIR domain in solution or using yeast 2-hybrid, mutations of surface-exposed residues in the AE interface prevent the cell-death autoactive phenotype. In addition, mutation of residues known to be important in the cell-death signalling function of the flax L6 TIR domain were also shown to be required for RPV1 TIR domain mediated cell-death. Our data demonstrate that multiple TIR domain surfaces control the cell-death function of the RPV1 TIR domain and we suggest that the conserved AE interface may have a general function in TIR-NLR signalling.

Off-Specular Synchrotron Moessbauer Reflectometry: A Novel Tool for Studying the Domain Structure in Antiferromagnetic Multilayers

Energy Technology Data Exchange (ETDEWEB)

Nagy, D. L.; Bottyan, L.; Deak, L. [KFKI Research Institute for Particle and Nuclear Physics (Hungary); Degroote, B.; Dekoster, J. [K.U. Leuven, Instituut voor Kern- en Stralingsfysica (Belgium); Leupold, O. [European Synchrotron Radiation Facility (France); Major, M. [KFKI Research Institute for Particle and Nuclear Physics (Hungary); Meersschaut, J. [K.U. Leuven, Instituut voor Kern- en Stralingsfysica (Belgium); Rueffer, R. [European Synchrotron Radiation Facility (France); Szilagyi, E. [KFKI Research Institute for Particle and Nuclear Physics (Hungary); Vantomme, A. [K.U. Leuven, Instituut voor Kern- en Stralingsfysica (Belgium)

2002-06-15

The off-specular (diffuse) nuclear resonant reflectivity of synchrotron radiation is a sensitive measure of the lateral autocorrelation of the magnetisation in thin films and multilayers. The width of the diffuse scattering peak measured at an electronically forbidden reflection is inversely proportional to the in-plane correlation length of the magnetisation direction. The average size of the in-plane antiferromagnetic domains is determined in different states of the same Fe/Cr superlattice. The hyperfine magnetic fields in coexisting small and large domains are measured independently.

Evolution of the RNase P RNA structural domain in Leptospira spp.

Science.gov (United States)

Ravishankar, Vigneshwaran; Ahmed, Ahmed; Sivagnanam, Ulaganathan; Muthuraman, Krishnaraja; Karthikaichamy, Anbarasu; Wilson, Herald A; Devendran, Ajay; Hartskeerl, Rudy A; Raj, Stephen M L

2014-12-01

We have employed the RNase P RNA (RPR) gene, which is present as single copy in chromosome I of Leptospira spp. to investigate the phylogeny of structural domains present in the RNA subunit of the tRNA processing enzyme, RNase P. RPR gene sequences of 150 strains derived from NCBI database along with sequences determined from 8 reference strains were examined to fathom strain specific structural differences present in leptospiral RPR. Sequence variations in the RPR gene impacted on the configuration of loops, stems and bulges found in the RPR highlighting species and strain specific structural motifs. In vitro transcribed leptospiral RPR ribozymes are demonstrated to process pre-tRNA into mature tRNA in consonance with the positioning of Leptospira in the taxonomic domain of bacteria. RPR sequence datasets used to construct a phylogenetic tree exemplified the segregation of strains into their respective lineages with a (re)speciation of strain SH 9 to Leptospira borgpetersenii, strains Fiocruz LV 3954 and Fiocruz LV 4135 to Leptospira santarosai, strain CBC 613 to Leptospira kirschneri and strain HAI 1536 to Leptospira noguchii. Furthermore, it allowed characterization of an isolate P2653, presumptively characterized as either serovar Hebdomadis, Kremastos or Longnan to Leptospira weilii, serovar Longnan. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor (HLTF) and Its Functional Implication in DNA Damage Tolerance.

Science.gov (United States)

Hishiki, Asami; Hara, Kodai; Ikegaya, Yuzu; Yokoyama, Hideshi; Shimizu, Toshiyuki; Sato, Mamoru; Hashimoto, Hiroshi

2015-05-22

HLTF (helicase-like transcription factor) is a yeast RAD5 homolog found in mammals. HLTF has E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. HLTF has an N-terminal domain that has been designated the HIRAN (HIP116 and RAD5 N-terminal) domain. The HIRAN domain has been hypothesized to play a role in DNA binding; however, the structural basis of, and functional evidence for, the HIRAN domain in DNA binding has remained unclear. Here we show for the first time the crystal structure of the HIRAN domain of human HLTF in complex with DNA. The HIRAN domain is composed of six β-strands and two α-helices, forming an OB-fold structure frequently found in ssDNA-binding proteins, including in replication factor A (RPA). Interestingly, this study reveals that the HIRAN domain interacts with not only with a single-stranded DNA but also with a duplex DNA. Furthermore, the structure unexpectedly clarifies that the HIRAN domain specifically recognizes the 3'-end of DNA. These results suggest that the HIRAN domain functions as a sensor to the 3'-end of the primer strand at the stalled replication fork and that the domain facilitates fork regression. HLTF is recruited to a damaged site through the HIRAN domain at the stalled replication fork. Furthermore, our results have implications for the mechanism of template switching. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

ProteinSplit: splitting of multi-domain proteins using prediction of ordered and disordered regions in protein sequences for virtual structural genomics

International Nuclear Information System (INIS)

Wyrwicz, Lucjan S; Koczyk, Grzegorz; Rychlewski, Leszek; Plewczynski, Dariusz

2007-01-01

The annotation of protein folds within newly sequenced genomes is the main target for semi-automated protein structure prediction (virtual structural genomics). A large number of automated methods have been developed recently with very good results in the case of single-domain proteins. Unfortunately, most of these automated methods often fail to properly predict the distant homology between a given multi-domain protein query and structural templates. Therefore a multi-domain protein should be split into domains in order to overcome this limitation. ProteinSplit is designed to identify protein domain boundaries using a novel algorithm that predicts disordered regions in protein sequences. The software utilizes various sequence characteristics to assess the local propensity of a protein to be disordered or ordered in terms of local structure stability. These disordered parts of a protein are likely to create interdomain spacers. Because of its speed and portability, the method was successfully applied to several genome-wide fold annotation experiments. The user can run an automated analysis of sets of proteins or perform semi-automated multiple user projects (saving the results on the server). Additionally the sequences of predicted domains can be sent to the Bioinfo.PL Protein Structure Prediction Meta-Server for further protein three-dimensional structure and function prediction. The program is freely accessible as a web service at http://lucjan.bioinfo.pl/proteinsplit together with detailed benchmark results on the critical assessment of a fully automated structure prediction (CAFASP) set of sequences. The source code of the local version of protein domain boundary prediction is available upon request from the authors

Magnetic domain structure and magnetically-induced reorientation in Ni–Mn–Ga magnetic shape memory alloy

Czech Academy of Sciences Publication Activity Database

Heczko, Oleg; Bradshaw, V.

2017-01-01

Roč. 131, č. 4 (2017), s. 1063-1065 ISSN 0587-4246 R&D Projects: GA ČR GA15-00262S Institutional support: RVO:68378271 Keywords : magnetic shape memory effect * magnetic domain structure * 3D visualization * domain mirroring Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 0.469, year: 2016

Structure of a financial cross-correlation matrix under attack

Science.gov (United States)

Lim, Gyuchang; Kim, SooYong; Kim, Junghwan; Kim, Pyungsoo; Kang, Yoonjong; Park, Sanghoon; Park, Inho; Park, Sang-Bum; Kim, Kyungsik

2009-09-01

We investigate the structure of a perturbed stock market in terms of correlation matrices. For the purpose of perturbing a stock market, two distinct methods are used, namely local and global perturbation. The former involves replacing a correlation coefficient of the cross-correlation matrix with one calculated from two Gaussian-distributed time series while the latter reconstructs the cross-correlation matrix just after replacing the original return series with Gaussian-distributed time series. Concerning the local case, it is a technical study only and there is no attempt to model reality. The term ‘global’ means the overall effect of the replacement on other untouched returns. Through statistical analyses such as random matrix theory (RMT), network theory, and the correlation coefficient distributions, we show that the global structure of a stock market is vulnerable to perturbation. However, apart from in the analysis of inverse participation ratios (IPRs), the vulnerability becomes dull under a small-scale perturbation. This means that these analysis tools are inappropriate for monitoring the whole stock market due to the low sensitivity of a stock market to a small-scale perturbation. In contrast, when going down to the structure of business sectors, we confirm that correlation-based business sectors are regrouped in terms of IPRs. This result gives a clue about monitoring the effect of hidden intentions, which are revealed via portfolios taken mostly by large investors.

Phase domain structures in cylindrical magnets under conditions of a first-order magnetic phase transition

International Nuclear Information System (INIS)

Dzhezherya, Yu.I.; Klymuk, O.S.

2011-01-01

The magnetic and resonance properties of cylindrical magnets at first-order phase transition from paramagnetic to ferromagnetic state were theoretically studied. It has been shown that in the external magnetic field directed perpendicularly to the rotation axis, formation of a specific domain structure of paramagnetic and ferromagnetic layers can be energetically favorable. The parameters of cylindrical phase domains as well as their dependences on temperature, magnetic field and material characteristics have been calculated. Peculiarities of the magnetic resonance spectra appearing as a result of the phase domain formation have been considered. Dependence of the resonance field of the system of ferromagnetic domains on magnetization and temperature has been obtained. - Highlights: → Parameters of the equilibrium system of cylindrical phase domains are calculated. → The range of fields for PM and FM phases coexistence is found. → FMR field of the disk domains is found to be lower than that of the PMR field.→ The resonance field increases with the decrease of temperature lower than T || .

Strain engineering and one-dimensional organization of metal-insulator domains in single-crystal vanadium dioxide beams.

Science.gov (United States)

Cao, J; Ertekin, E; Srinivasan, V; Fan, W; Huang, S; Zheng, H; Yim, J W L; Khanal, D R; Ogletree, D F; Grossman, J C; Wu, J

2009-11-01

Correlated electron materials can undergo a variety of phase transitions, including superconductivity, the metal-insulator transition and colossal magnetoresistance. Moreover, multiple physical phases or domains with dimensions of nanometres to micrometres can coexist in these materials at temperatures where a pure phase is expected. Making use of the properties of correlated electron materials in device applications will require the ability to control domain structures and phase transitions in these materials. Lattice strain has been shown to cause the coexistence of metallic and insulating phases in the Mott insulator VO(2). Here, we show that we can nucleate and manipulate ordered arrays of metallic and insulating domains along single-crystal beams of VO(2) by continuously tuning the strain over a wide range of values. The Mott transition between a low-temperature insulating phase and a high-temperature metallic phase usually occurs at 341 K in VO(2), but the active control of strain allows us to reduce this transition temperature to room temperature. In addition to device applications, the ability to control the phase structure of VO(2) with strain could lead to a deeper understanding of the correlated electron materials in general.

Monte Carlo simulation for thermal assisted reversal process of micro-magnetic torus ring with bistable closure domain structure

Energy Technology Data Exchange (ETDEWEB)