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Sample records for ceroid lipofuscinosis proteins

  1. Juvenil neuronal ceroid lipofuscinosis

    DEFF Research Database (Denmark)

    Ostergaard, J R; Hertz, Jens Michael

    1998-01-01

    Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The diseases can be differentiated into several subgroups according to age of onset, the clinical picture...

  2. Ceroid-lipofuscinosis in border collie dogs.

    Science.gov (United States)

    Taylor, R M; Farrow, B R

    1988-01-01

    Five Border Collie dogs with ceroid-lipofuscinosis developed progressive neurological disease between 18 and 22 months of age. These dogs had behavioural abnormalities, gait and visual deficits and became progressively demented. All dogs examined had common ancestors. Light microscopic examination of tissues demonstrated extensive accumulation of granular, sudan black-staining autofluorescent material in the cytoplasm of neurones, retinal ganglion cells and some visceral cells. At ultrastructural examination inclusions of variable morphology were observed. PMID:3376765

  3. Novel interactions of CLN5 support molecular networking between Neuronal Ceroid Lipofuscinosis proteins

    Directory of Open Access Journals (Sweden)

    Jalanko Anu

    2009-11-01

    Full Text Available Abstract Background Neuronal ceroid lipofuscinoses (NCLs comprise at least eight genetically characterized neurodegenerative disorders of childhood. Despite of genetic heterogeneity, the high similarity of clinical symptoms and pathology of different NCL disorders suggest cooperation between different NCL proteins and common mechanisms of pathogenesis. Here, we have studied molecular interactions between NCL proteins, concentrating specifically on the interactions of CLN5, the protein underlying the Finnish variant late infantile form of NCL (vLINCLFin. Results We found that CLN5 interacts with several other NCL proteins namely, CLN1/PPT1, CLN2/TPP1, CLN3, CLN6 and CLN8. Furthermore, analysis of the intracellular targeting of CLN5 together with the interacting NCL proteins revealed that over-expression of PPT1 can facilitate the lysosomal transport of mutated CLN5FinMajor, normally residing in the ER and in the Golgi complex. The significance of the novel interaction between CLN5 and PPT1 was further supported by the finding that CLN5 was also able to bind the F1-ATPase, earlier shown to interact with PPT1. Conclusion We have described novel interactions between CLN5 and several NCL proteins, suggesting a modifying role for these proteins in the pathogenesis of individual NCL disorders. Among these novel interactions, binding of CLN5 to CLN1/PPT1 is suggested to be the most significant one, since over-expression of PPT1 was shown to influence on the intracellular trafficking of mutated CLN5, and they were shown to share a binding partner outside the NCL protein spectrum.

  4. Novel CLN1 mutation with atypical juvenile neuronal ceroid lipofuscinosis

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    Arif Khan

    2013-01-01

    Full Text Available We detected a novel CLN1 gene mutation (p.Arg151X, heterogenous in a 12-year-old boy. Low level of palmitoyl protein thioesterase and granular inclusion pattern in lymphocytes were also consistent with infantile Neuronal ceroid lipofuscinosis (INCL. However, the clinical phenotype was that of atypical juvenile neuronal ceroid lipofuscinosis (JNCL and consisted of progressive visual loss from the age of 8 years. His visual acuity was 6/60 in both eyes at first presentation, 6/36 one month later, then 6/6 (right eye, and 6/60 (left eye 6 months later. However, after 4 months, visual acuity dropped to 6/60 in both eyes and at last follow-up, it was 6/60 (right eye and 3/60 (left eye. Visual hallucinations were also reported. Persistent normal fundi findings, normal electroretinogram (ERG, and delayed visual evoked potentials (VEP were suggestive of non-retinal adolescence form/atypical JNCL. Visual loss in JNCL is secondary to retinal dystrophy. Our observations suggest that JNCL should be considered in any children presenting with bilateral progressive visual loss even with normal fundi and/or delayed VEP. Electron microscopy of buffy coat and palmitoyl protein thioesterase enzyme study are useful tools in diagnosis. Pertinent issues regarding clinical symptomatology, ophthalmologic findings, and laboratory results are discussed.

  5. OPTICAL COHERENCE TOMOGRAPHY IN JUVENILE NEURONAL CEROID LIPOFUSCINOSIS

    DEFF Research Database (Denmark)

    Hansen, Michael S; Hove, Marianne Nørgaard; Jensen, Hanne;

    2016-01-01

    PURPOSE: To report optical coherence tomography findings obtained in two patients with juvenile neuronal ceroid lipofuscinosis. METHODS: Two case reports. RESULTS: Two 7-year-old girls presented with decreased visual acuity, clumsiness, night blindness, and behavioral problems. Optical coherence...... tomography showed an overall reduction in thickness of the central retina, as well as the outer and the inner retinal layers. The degenerative retinal changes were the same, despite different mutations in the CLN3 gene. CONCLUSION: In these rare cases of juvenile neuronal ceroid lipofuscinosis, optical...

  6. Juvenile neuronal ceroid lipofuscinosis (Batten disease): current insights

    OpenAIRE

    Ostergaard, John

    2016-01-01

    John R Ostergaard Department of Paediatrics, Aarhus University Hospital, Centre for Rare Diseases, Aarhus, Denmark Abstract: The present review is focused on juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease) due to a mutation in CLN3. Functional vision impairment occurring around 5–6 years of age is the first symptom in more than 80% of patients. Approximately 2 years later (though sometimes simultaneously), obvious signs of cognitive impairment appear. Behavior problem...

  7. Multifocal Retinopathy in Dachshunds with CLN2 Neuronal Ceroid Lipofuscinosis

    OpenAIRE

    Whiting, Rebecca E. H.; Pearce, Jacqueline W.; Castaner, Leilani J.; Jensen, Cheryl A.; Katz, Rebecca J.; Gilliam, Douglas H.; Katz, Martin L.

    2015-01-01

    The CLN2 form of neuronal ceroid lipofuscinosis is an autosomal recessively inherited lysosomal storage disease that is characterized by progressive vision loss culminating in blindness, cognitive and motor decline, neurodegeneration, and premature death. CLN2 disease results from mutations in the gene that encodes the soluble lysosomal enzyme tripeptidyl peptidase-1. A null mutation in the TPP1 gene encoding this enzyme causes a CLN2-like disease in Dachshunds. Dachshunds that are homozygous...

  8. [The canine neuronal ceroid-lipofuscinosis: a review].

    Science.gov (United States)

    Karli, P; Karol, A; Oevermann, A; Drögemüller, C; Gorgas, D; Henke, D

    2014-09-01

    The present article gives a survey over the current scientific knowledge of the canine neuronal ceroid-lipofuscinosis (NCL). NCL is a heterogenous group of lysosomal storage diseases in humans and animals. In consequence of a gene mutation, there is an accumulation of ceroid-lipofuscin in neurons, cells of the retina and the skin and other cells. The stored ceroid-lipofuscin in neurons leads to an impaired cell function and subsequently to cell death. Recently, the underlying genetic defect was discovered in several dog breeds. Genetic testing permits an ante mortem diagnosis of the disease, which up to now was only possible with a positive biopsy result. Another advantage is the identification of carrier animals to eliminate the deleterious alleles. PMID:25183673

  9. Use of model organisms for the study of neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Bond, Michael; Holthaus, Sophia-Martha Kleine; Tammen, Imke; Tear, Guy; Russell, Claire

    2013-11-01

    Neuronal ceroid lipofuscinoses are a group of fatal progressive neurodegenerative diseases predominantly affecting children. Identification of mutations that cause neuronal ceroid lipofuscinosis, and subsequent functional and pathological studies of the affected genes, underpins efforts to investigate disease mechanisms and identify and test potential therapeutic strategies. These functional studies and pre-clinical trials necessitate the use of model organisms in addition to cell and tissue culture models as they enable the study of protein function within a complex organ such as the brain and the testing of therapies on a whole organism. To this end, a large number of disease models and genetic tools have been identified or created in a variety of model organisms. In this review, we will discuss the ethical issues associated with experiments using model organisms, the factors underlying the choice of model organism, the disease models and genetic tools available, and the contributions of those disease models and tools to neuronal ceroid lipofuscinosis research. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease. PMID:23338040

  10. Neurobehavioral Features and Natural History of Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease)

    OpenAIRE

    Adams, Heather R.; Mink, Jonathan W.

    2013-01-01

    Juvenile neuronal ceroid lipofuscinosis is a childhood-onset neurodegenerative disease with prominent symptoms comprising a pediatric dementia syndrome: intellectual decline, mood and behavioral impairments, and loss of adaptive skills. We review the history of neurobehavioral features in juvenile neuronal ceroid lipofuscinosis and the work of the University of Rochester Batten Center to characterize the extent and progression of neurobehavioral symptoms over disease course, and discuss the r...

  11. Juvenile neuronal ceroid lipofuscinosis (Batten disease: current insights

    Directory of Open Access Journals (Sweden)

    Ostergaard JR

    2016-08-01

    Full Text Available John R Ostergaard Department of Paediatrics, Aarhus University Hospital, Centre for Rare Diseases, Aarhus, Denmark Abstract: The present review is focused on juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease due to a mutation in CLN3. Functional vision impairment occurring around 5–6 years of age is the first symptom in more than 80% of patients. Approximately 2 years later (though sometimes simultaneously, obvious signs of cognitive impairment appear. Behavior problems can occur in advance, especially in boys. These include anxious and depressed mood, aggressive behavior, and hallucinations, and even psychotic symptoms. Following the teens, severe dementia is present, including loss of memory, attention, and general reasoning abilities, as well as loss of independent adaptive skills such as mobility, feeding, and communicating. Sleep abnormalities, such as settling problems, nocturnal awakenings, and nightmares, are reported in more than half of patients. The vast majority, if not all, patients develop seizures, starting at approximately 10 years of age. Generalized tonic–clonic seizure occurs as the only type of seizure in approximately half of patients, and in combination with partial seizures in a third of patients. There seems to be no difference in seizure severity according to sex or genotype, and there is great variation in seizure activity among patients. Soon after diagnosis, patients begin to have slight ataxic symptoms, and at adolescence extrapyramidal symptoms (rigidity, bradykinesia, slow steps with flexion in hips and knees occur with increasing frequency. Chewing and swallowing difficulties emerge as well, and food intake is hampered in the late teens. Disabling periodically involuntary movements may occur as well. A progressive cardiac involvement with repolarization disturbances, ventricular hypertrophy, and sinus-node dysfunction, ultimately leading to severe bradycardia and/or other conduction abnormalities

  12. Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis

    OpenAIRE

    Roberts, Marie S.; Macauley, Shannon L.; Wong, Andrew M.; Yilmas, Denis; Hohm, Sarah; Cooper, Jonathan D.; Sands, Mark S.

    2012-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is a profoundly neurodegenerative disease of children caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). There is currently no effective therapy for this invariably fatal disease. To date, preclinical experiments using single treatments have resulted in incremental clinical improvements. Therefore, we determined the efficacy of CNS-directed AAV2/5-mediated gene therapy alone and in combination with the system...

  13. MRI findings in childhood with neuronal ceroid lipofuscinosis

    International Nuclear Information System (INIS)

    Objective: To characterize the MR imaging findings in different types of neuronal ceroid lipofuscinosis (NCL) in childhood. Methods: Six children with NCL and 6 age-matched control subjects were examined by using MRI. There was 2 patients with infantile NCL, 2 with late-infantile NCL, and 2 with juvenile NCL. Results: The cerebral atrophy was found in patients with infantile NCL, but the cerebellar atrophy was found in patients with late-infantile NCL and juvenile NCL; Hyperintensity in the centrum semiovale or periventricular white matter on T2WI was revealed in all cases; Decreased T2 signal was seen in the thalami in five patients, except for 1 juvenile NCL; Decreased T2 signal in the basal ganglia was seen in the 2 case with late-infantile NCL. No abnormal change was found in the control subjects. Conclusion: MRI is of great value in demonstrating the early changes of NCL. MRI especially facilitates the classification and early diagnosis of NCL

  14. MRI of neuronal ceroid lipofuscinosis. Pt. 1. Cranial MRI of 30 patients with juvenile neuronal ceroid lipofuscinosis

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    Autti, T. [Dept. of Pediatric Neurology, Children`s Hospital, Helsinki Univ. (Finland)]|[Dept. of Radiology, Helsinki Univ. Central Hospital (Finland); Raininko, R. [Dept. of Radiology, Helsinki Univ. Central Hospital (Finland); Santavuori, P. [Dept. of Pediatric Neurology, Children`s Hospital, Helsinki Univ. (Finland); Vanhanen, S.L. [Dept. of Pediatric Neurology, Children`s Hospital, Helsinki Univ. (Finland)

    1996-07-01

    We studied 30 patients with juvenile neuronal ceroid lipofuscinosis (JNCL). The patients (aged 6-25 years) and 43 age-matched healthy volunteers underwent MRI. After visual assessment, the signal intensity was measured on T2-weighted images in numerous locations. The thickness of the cortex and corpus callosum and the dimensions of the brain stem were measured. Mild to moderate cerebral atrophy was found in 14 to 30 patients, most of them over 14 years of age; 5 older patients had mild to moderate cerebellar atrophy. There was reduction in the size of the corpus callosum and brain stem. The thalamus, caudate nucleus and putamen appeared to give low signal in patients form the ages of 7, 11 and 11 years, respectively. In contrast, the signal intensity measured from the thalamus in these patients showed only a slight (insignificant) decrease compared with controls. The most significant alteration, an increase in measured signal intensity, was found in the white matter (P<0.0001), even in the youngest patients. The MRI findings correlated significantly with decreased intelligence, speech disturbances and motor problems. Although MRI findings in JNCL do not appear very specific and the visual changes develop relatively late, the absence of pathological MRI findings in the very early stage of the disease may play a part in differnetial diagnosis of the different types of NCL. Furthermore, the MRI findings may be used in assessing severity and prognosis, particularly in young patients. (orig.)

  15. MRI of neuronal ceroid lipofuscinosis. Pt. 1. Cranial MRI of 30 patients with juvenile neuronal ceroid lipofuscinosis

    International Nuclear Information System (INIS)

    We studied 30 patients with juvenile neuronal ceroid lipofuscinosis (JNCL). The patients (aged 6-25 years) and 43 age-matched healthy volunteers underwent MRI. After visual assessment, the signal intensity was measured on T2-weighted images in numerous locations. The thickness of the cortex and corpus callosum and the dimensions of the brain stem were measured. Mild to moderate cerebral atrophy was found in 14 to 30 patients, most of them over 14 years of age; 5 older patients had mild to moderate cerebellar atrophy. There was reduction in the size of the corpus callosum and brain stem. The thalamus, caudate nucleus and putamen appeared to give low signal in patients form the ages of 7, 11 and 11 years, respectively. In contrast, the signal intensity measured from the thalamus in these patients showed only a slight (insignificant) decrease compared with controls. The most significant alteration, an increase in measured signal intensity, was found in the white matter (P<0.0001), even in the youngest patients. The MRI findings correlated significantly with decreased intelligence, speech disturbances and motor problems. Although MRI findings in JNCL do not appear very specific and the visual changes develop relatively late, the absence of pathological MRI findings in the very early stage of the disease may play a part in differnetial diagnosis of the different types of NCL. Furthermore, the MRI findings may be used in assessing severity and prognosis, particularly in young patients. (orig.)

  16. A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs.

    Science.gov (United States)

    Melville, Scott A; Wilson, Carmen L; Chiang, Chiu S; Studdert, Virginia P; Lingaas, Frode; Wilton, Alan N

    2005-09-01

    Neuronal ceroid lipofuscinosis (NCL) is a neurodegenerative disease found in Border collie dogs, humans, and other animals. Disease gene studies in humans and animals provided candidates for the NCL gene in Border collies. A combination of linkage analysis and comparative genomics localized the gene to CFA22 in an area syntenic to HSA13q that contains the CLN5 gene responsible for the Finnish variant of human late infantile NCL. Sequencing of CLN5 revealed a nonsense mutation (Q206X) within exon 4 that correlated with NCL in Border collies. This truncation mutation should result in a protein product of a size similar to that of some mutations identified in human CLN5 and therefore the Border collie may make a good model for human NCL. A simple test was developed to enable screening of the Border collie population for carriers so the disease can be eliminated as a problem in the breed. PMID:16033706

  17. Magnetic resonance imaging of neuronal ceroid lipofuscinosis in a border collie.

    Science.gov (United States)

    Koie, Hiroshi; Shibuya, Hisashi; Sato, Tsuneo; Sato, Akane; Nawa, Koji; Nawa, Yuko; Kitagawa, Masato; Sakai, Manabu; Takahashi, Tomoko; Yamaya, Yoshiki; Yamato, Osamu; Watari, Toshihiro; Tokuriki, Mikihiko

    2004-11-01

    A castrated male border collie 23 months of age weighing 19.4 kg was referred to the Animal Medical Center of Nihon University with complaints of visual disturbance and behavioral abnormality, hyperacusis and morbid fear. The MRI examination revealed the slight dilated cerebral sulci and cerebellar fissures and left ventricular enlargement. This is the first report of MRI findings of canine neuronal ceroid lipofuscinosis. PMID:15585966

  18. Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum

    OpenAIRE

    Phillips, Jonathan E.; Gomer, Richard H.

    2014-01-01

    Neuronal ceroid lipofuscinosis (NCL) is the most common childhood-onset neurodegenerative disease. NCL is inevitably fatal, and there is currently no treatment available. Children with NCL show a progressive decline in movement, vision and mental abilities, and an accumulation of autofluorescent deposits in neurons and other cell types. Late-infantile NCL is caused by mutations in the lysosomal protease tripeptidyl peptidase 1 (TPP1). TPP1 cleaves tripeptides from the N-terminus of proteins i...

  19. Antigen presenting cell abnormalities in the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Hersrud, Samantha L; Kovács, Attila D; Pearce, David A

    2016-07-01

    Mutations of the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive lysosomal storage disorder that causes progressive neurodegeneration in children and adolescents. There is evidence of immune system involvement in pathology that has been only minimally investigated. We characterized bone marrow stem cell-derived antigen presenting cells (APCs), peritoneal macrophages, and leukocytes from spleen and blood, harvested from the Cln3(-/-) mouse model of JNCL. We detected dramatically elevated CD11c surface levels and increased total CD11c protein in Cln3(-/-) cell samples compared to wild type. This phenotype was specific to APCs and also to a loss of CLN3, as surface levels did not differ from wild type in other leukocyte subtypes nor in cells from two other NCL mouse models. Subcellularly, CD11c was localized to lipid rafts, indicating that perturbation of surface levels is attributable to derangement of raft dynamics, which has previously been shown in Cln3 mutant cells. Interrogation of APC function revealed that Cln3(-/-) cells have increased adhesiveness to CD11c ligands as well as an abnormal secretory pattern that closely mimics what has been previously reported for Cln3 mutant microglia. Our results show that CLN3 deficiency alters APCs, which can be a major contributor to the autoimmune response in JNCL. PMID:27101989

  20. Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis

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    Tuulia Huhtala

    2012-01-01

    Full Text Available Infantile neuronal ceroid lipofuscinosis (INCL is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1 is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles.

  1. Imaging gene delivery in a mouse model of congenital neuronal ceroid lipofuscinosis

    OpenAIRE

    Pike, Lisa S.; Tannous, Bakhos A; Deliolanis, Nikolaos C.; Hsich, Gary; Morse, Danielle; Tung, Ching-Hsuan; Sena-Esteves, Miguel; Breakefield, Xandra O.

    2011-01-01

    Adeno-associated virus (AAV) mediated gene replacement for lysosomal disorders have been spurred by the ability of some serotypes to efficiently transduce neurons in the brain and by the ability of lysosomal enzymes to cross-correct among cells. Here, we explored enzyme replacement therapy in a knock-out mouse model of congenital neuronal ceroid lipofuscinosis (NCL), the most severe of the NCLs in humans. The missing protease in this disorder, cathepsin D (CathD) has high levels in the centra...

  2. Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.

    Science.gov (United States)

    Geraets, Ryan D; Koh, Seung yon; Hastings, Michelle L; Kielian, Tammy; Pearce, David A; Weimer, Jill M

    2016-01-01

    The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset. Though the disease phenotypes may vary in their age and order of presentation, all typically include progressive visual deterioration and blindness, cognitive impairment, motor deficits and seizures. Pathological hallmarks of NCLs include the accumulation of storage material or ceroid in the lysosome, progressive neuronal degeneration and massive glial activation. Advances have been made in genetic diagnosis and counseling for families. However, comprehensive treatment programs that delay or halt disease progression have been elusive. Current disease management is primarily targeted at controlling the symptoms rather than "curing" the disease. Recognizing the growing need for transparency and synergistic efforts to move the field forward, this review will provide an overview of the therapeutic approaches currently being pursued in preclinical and clinical trials to treat different forms of NCL as well as provide insight to novel therapeutic approaches in development for the NCLs. PMID:27083890

  3. CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis).

    Science.gov (United States)

    Kohlschütter, Alfried; Schulz, Angela

    2016-06-01

    CLN2 disease is an inherited metabolic storage disorder caused by the deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). The disease affects mainly the brain and the retina and is characterized by progressive dysfunction of the central nervous system, leading to dementia, epilepsy, loss of motor function and blindness. The classical late infantile type begins at around three years of age with epilepsy and/or a standstill of psychomotor development, followed by a rapid loss of all abilities and death in childhood. A late onset form in a small proportion of patients starts at the age of 4 to 10 years, but also leads to severe neurological deterioration. The deficiency of TPP1 causes the lysosomal accumulation of a material called ceroid lipofuscin. The natural substrate of TPP1 is not known, nor is the connection between storage process and neurodegeneration, which is characterized by loss of neurons. Among various experimental approaches to treatment, enzyme replacement therapy (ERT) and gene therapy have developed remarkably. Enzyme delivery through the cerebrospinal fluid led to wide distribution of enzyme activity in the brain and to attenuated neuropathology and disease progression in a TPP1-deficient mouse model as well as in a natural TPP1-deficient dog model. Safety of the intrathecal delivery, pharmacokinetics, and tissue distribution of the administered enzyme studied in non-human primates were encouraging, and a phase I/II clinical trial for intraventricular ERT in CLN2 patients is ongoing. A second approach uses intracerebral injection of viral vectors containing normal coding segments of the CLN2 gene. In a CLN2 mouse model, this procedure resulted in cerebral enzyme expression, reduced brain pathology and increased survival. A small number of patients have been treated the same way using an AAV2-vector for gene transfer to the brain. Although there were no serious adverse events unequivocally attributable to the vector used, there were

  4. Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late infantile neuronal ceroid lipofuscinosis

    OpenAIRE

    Sleat, David E.; El-Banna, Mukarram; Sohar, Istvan; Kim, Kwi-Hye; Dobrenis, Kostantin; Walkley, Steven U.; Lobel, Peter

    2008-01-01

    Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary neurodegenerative disease of childhood that is caused by mutations in the gene (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is fatal and there is no treatment of demonstrated efficacy in affected children but preclinical studies with AAV-mediated gene therapy have demonstrated promise in a mouse model. Here, we have generated mouse CLN2 mutants that express different amounts of TPPI...

  5. Neuronal Ceroid-lipofuscinosis with prominent chorea and without visual manifestations: a case report

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    Luciano de Souza Queiroz

    1979-03-01

    Full Text Available A case of neuronal ceroid-lipofuscinosis (NCL is reported in a 11-year-old girl, whose main symptoms were progressive dementia since the age of 4 years and choreic movements since age 10. Seizures, myoclonus and visual deterioration were absent and optic fundi were normal. A cerebral biopsy disclosed two basic types of stored substance in the cytoplasm of neurons: a severely balloned nerve cells in cortical layers HI and V contained a non-autofluorescent material, which stained with PAS and Sudan Black B in frozen, but not in paraffin sections; ultrastructurally, these neurons showed abundant corpuscles similar to the membranous cytoplasmic bodies of Tay-Sachs disease and, in smaller amounts, also zebra bodies; b slightly distended or non-distended neurons in all layers contained lipopigment granules, which were autofluorescent, PAS-positive and sudanophil in both frozen and paraffin sections; their ultrastructure was closely comparable to that of lipofuscin. Similar bodies were found in the swollen segments of axons and in a few astrocytes and endothelial cells. The histochemical and ultrastructural demonstration of large amounts of lipopigments allows a presumptive classification of the case as NCL. However, the presence of involuntary movements, the absence of visual disturbances and the unusual ultrastructural features place the patient into a small heterogeneous group within the NCL. A better classification of such unique instances of the disease must await elucidation of the basic enzymatic defects.

  6. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.

    LENUS (Irish Health Repository)

    Arsov, Todor

    2011-05-13

    The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.

  7. Gene expression profiling in a mouse model of infantile neuronal ceroid lipofuscinosis reveals upregulation of immediate early genes and mediators of the inflammatory response

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    Hofmann Sandra L

    2007-11-01

    Full Text Available Abstract Background The infantile form of neuronal ceroid lipofuscinosis (also known as infantile Batten disease is caused by hereditary deficiency of a lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1, and is characterized by severe cortical degeneration with blindness and cognitive and motor dysfunction. The PPT1-deficient knockout mouse recapitulates the key features of the disorder, including seizures and death by 7–9 months of age. In the current study, we compared gene expression profiles of whole brain from PPT1 knockout and normal mice at 3, 5 and 8 months of age to identify temporal changes in molecular pathways implicated in disease pathogenesis. Results A total of 267 genes were significantly (approximately 2-fold up- or downregulated over the course of the disease. Immediate early genes (Arc, Cyr61, c-fos, jun-b, btg2, NR4A1 were among the first genes upregulated during the presymptomatic period whereas immune response genes dominated at later time points. Chemokine ligands and protease inhibitors were among the most transcriptionally responsive genes. Neuronal survival factors (IGF-1 and CNTF and a negative regulator of neuronal apoptosis (DAP kinase-1 were upregulated late in the course of the disease. Few genes were downregulated; these included the α2 subunit of the GABA-A receptor, a component of cortical and hippocampal neurons, and Hes5, a transcription factor important in neuronal differentiation. Conclusion A molecular description of gene expression changes occurring in the brain throughout the course of neuronal ceroid lipofuscinosis suggests distinct phases of disease progression, provides clues to potential markers of disease activity, and points to new targets for therapy.

  8. A case of neuronal ceroid-lipofuscinosis (late infantile type) followed by CT and electrophysiological examinations for 7 years

    International Nuclear Information System (INIS)

    A patient with late infantile type of neuronal ceroid-lipofuscinosis was followed by CT and electrophysiological examinations for 7 years. CT showed that brain atrophy started in the cerebellum and the brain stem and progressed to the cerebral cortex later. In EEG, diffuse and high voltage slow waves seen at the first stage were decreased in the voltage, and multiple focal spikes appeared. They disappeared at the terminal stage. Giant evoked potentials in the visual evoked response and the somatosensory evoked potential were present initially, but they were decreased later and finally there was no response. The origin of myoclonus frequently observed at the terminal stage was studied by myoclonus related cortical potentials. The first appearance of myoclonus in the sternocleidomastoid muscle suggested that the myoclonus might have originated from a lesion near the accesory nucleus in the brain stem. (author)

  9. Parent-reported benefits of flupirtine in juvenile neuronal ceroid lipofuscinosis (Batten disease; CLN3) are not supported by quantitative data

    OpenAIRE

    Cialone, Jennifer; Augustine, Erika F.; Newhouse, Nicole; Adams, Heather; Vierhile, Amy; Marshall, Frederick J.; DE BLIECK, ELISABETH A; Kwon, Jennifer; Rothberg, Paul G.; Mink, Jonathan W.

    2011-01-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3 disease; Batten disease) is an autosomal recessive neurodegenerative disease of childhood that typically presents at school age with vision loss followed by progressive cognitive decline, motor dysfunction, seizures, and behavior problems. No therapy has been shown to slow the progression of disease in JNCL patients, and all current treatments are symptomatic. Flupirtine has been shown in vitro to reduce apoptosis in CLN3 lymphocytes. Based ...

  10. CNS-Expressed Cathepsin D Prevents Lymphopenia in a Murine Model of Congenital Neuronal Ceroid Lipofuscinosis

    OpenAIRE

    Shevtsova, Zinayida; Garrido, Manuel; Weishaupt, Jochen; Saftig, Paul; Bähr, Mathias; Lühder, Fred; Kügler, Sebastian

    2010-01-01

    Deficiency in Cathepsin D (CtsD), the major cellular lysosomal aspartic proteinase, causes the congenital form of neuronal ceroid lipofuscinoses (NCLs). CtsD-deficient mice show severe visceral lesions like lymphopenia in addition to their central nervous system (CNS) phenotype of ceroid accumulation, microglia activation, and seizures. Here we demonstrate that re-expression of CtsD within the CNS but not re-expression of CtsD in visceral organs prevented both central and visceral pathologies...

  11. Comparison of brain perfusion SPECT and MRI findings in children with neuronal ceroid-lipofuscinosis and in their families

    International Nuclear Information System (INIS)

    Neuronal ceroid-lipofuscinoses (NCL) are among the progressive encephalopathies of childhood that are inherited in an autosomal recessive manner. In this study we specifically aimed to investigate any white-matter changes in the carriers (parents) and the healthy siblings of individuals with neuronal ceroid lipofuscinosis disease and whether we may be able to predict the occurrence of any neurological symptoms in healthy children in the future thus enabling early management. Since the NCLs are genetically determined diseases, we investigated fifteen individuals in three families that had diseased children of the juvenile type, with brain perfusion SPECT and MRI. Brain perfusion SPECT was performed after administering 222-555 MBq (6-15 mCi) Tc-99m hexamethyl-propylene amine oxime (HMPAO) intravenously in a dimmed and quiet room. Imaging was performed at least one hour after injection, with a three headed gamma camera equipped with high resolution collimators. A Metz filter (FWHM: 11 mm) was used for processing. Cranial MRI was performed with an imager operating at 1.5 Tesla. Spin-echo T1- and T2-weighted and FLAIR slices were obtained for each individual. In all of the five diseased children we observed pathologic findings both on MRI and Tc-99m HMPAO SPECT. The findings on MRI were mainly features of cerebral and cerebellar atrophy and the observations on Tc-99m HMPAO SPECT were regional perfusion abnormalities. We observed some structural abnormalities on MRI in four of the parents and two of the four healthy siblings. We also noted perfusion abnormalities on Tc-99m HMPAO SPECT in two of the parents and two of the healthy siblings. Because the disease is inherited in an autosomal recessive manner, the parents and the healthy siblings were not supposed to exhibit any demonstrable brain lesions, but the brain perfusion SPECT and MRI examinations clearly revealed multiple lesions in some of the parents and healthy siblings. Detailed neurological examinations of these

  12. Electrophysiological and cranial computed tomographical follow-up study on a case of late infantile ceroid lipofuscinosis

    International Nuclear Information System (INIS)

    Electrophysiological and cranial computed tomographical follow-up studies were carried out on a male suffering from late infantile ceroid lipofuscinosis (CLF) during the ages from 3 to 7 and the following results were obtained. 1. Electroencephalographic findings. (1) Spike and slow waves were noted in the occipital area initially when he was 3 years old, and these abnormalities spread rapidly to entire cereberum thereafter. (2) Occipital spikes and spike-slow waves synchronized with low frequency photic stimuli (1 -- 3 c/s) were confirmed as an important diagnostic indicator of CLS. 2. Other electrophysilogical findings. Findings of both silent electroretinogram and hyper-responded sensory evoked potential by median nerve stimulation, performed when he was 5 years old, were also important diagnostic indicators in addition to EEG findings. 3. Cranial computed tomography (CCT), CCT revealed mild cortical atrophy of the cereberum and cerebellum when he was 4 years old. Yearly CCT examinations from 4 to 7 years of age showed marked progressive diffuse atrophy, suggesting more severe involvement of gray matter than white matter. (author)

  13. Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy: clinical and pathological study of four cases

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    Luciano de Souza Queiroz

    1974-03-01

    Full Text Available Neuronal ceroid-lipofuscinosis (NCL is a recent term, proposed for acurate designation of the late-onset types of Amaurotic Family Idiocy (AFI. Histopathology shows ubiquitous intraneuronal accumulation of lipopigments, being the most important factor for characterization of the entity at present time. Biochemical changes and pathogenesis are obscure. NCL is in contrast to the infantile type of AFI (Tay-Sachs disease, in which intraneuronal accumulation of gangliosides (sphingolipids is due to the well known deficiency of a lysosomal enzyme. The authors report on four cases of NCL, two brothers of the late infantile (Jansky-Bielschowsky type and a brother and a sister of the juvenile (Spielmeyer-Sjögren type. One autopsy and three cortical biopsies revealed moderate to severe distention of the neurons by lipopigment, with nerve cell loss, gliosis and cerebral atrophy. Lipopigment was also increased in liver, heart and spleen. The patients were the first in Brazilian literature in whom the storage material was identified as lipopigment by histochemical methods. A brief summary of the clinical features of NCL is presented, and relevant problems are discussed, concerning interpretation of the nature of the storage material, and significance of the disease for gerontological research.

  14. Neuronal ceroid lipofuscinosis in Border Collie dogs in Japan: clinical and molecular epidemiological study (2000-2011).

    Science.gov (United States)

    Mizukami, Keijiro; Kawamichi, Takuji; Koie, Hiroshi; Tamura, Shinji; Matsunaga, Satoru; Imamoto, Shigeki; Saito, Miyoko; Hasegawa, Daisuke; Matsuki, Naoaki; Tamahara, Satoshi; Sato, Shigenobu; Yabuki, Akira; Chang, Hye-Sook; Yamato, Osamu

    2012-01-01

    Neuronal ceroid lipofuscinosis (NCL) is an inherited, neurodegenerative lysosomal disease that causes premature death. The present study describes the clinical and molecular epidemiologic findings of NCL in Border Collies in Japan for 12 years, between 2000 and 2011. The number of affected dogs was surveyed, and their clinical characteristics were analyzed. In 4 kennels with affected dogs, the dogs were genotyped. The genetic relationships of all affected dogs and carriers identified were analyzed. The survey revealed 27 affected dogs, but there was a decreasing trend at the end of the study period. The clinical characteristics of these affected dogs were updated in detail. The genotyping survey demonstrated a high mutant allele frequency in examined kennels (34.8%). The pedigree analysis demonstrated that all affected dogs and carriers in Japan are related to some presumptive carriers imported from Oceania and having a common ancestor. The current high prevalence in Japan might be due to an overuse of these carriers by breeders without any knowledge of the disease. For NCL control and prevention, it is necessary to examine all breeding dogs, especially in kennels with a high prevalence. Such endeavors will reduce NCL prevalence and may already be contributing to the recent decreasing trend in Japan. PMID:22919312

  15. Neuronal Ceroid Lipofuscinosis in Border Collie Dogs in Japan: Clinical and Molecular Epidemiological Study (2000–2011

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    Keijiro Mizukami

    2012-01-01

    Full Text Available Neuronal ceroid lipofuscinosis (NCL is an inherited, neurodegenerative lysosomal disease that causes premature death. The present study describes the clinical and molecular epidemiologic findings of NCL in Border Collies in Japan for 12 years, between 2000 and 2011. The number of affected dogs was surveyed, and their clinical characteristics were analyzed. In 4 kennels with affected dogs, the dogs were genotyped. The genetic relationships of all affected dogs and carriers identified were analyzed. The survey revealed 27 affected dogs, but there was a decreasing trend at the end of the study period. The clinical characteristics of these affected dogs were updated in detail. The genotyping survey demonstrated a high mutant allele frequency in examined kennels (34.8%. The pedigree analysis demonstrated that all affected dogs and carriers in Japan are related to some presumptive carriers imported from Oceania and having a common ancestor. The current high prevalence in Japan might be due to an overuse of these carriers by breeders without any knowledge of the disease. For NCL control and prevention, it is necessary to examine all breeding dogs, especially in kennels with a high prevalence. Such endeavors will reduce NCL prevalence and may already be contributing to the recent decreasing trend in Japan.

  16. Exome Sequencing Is an Efficient Tool for Variant Late-Infantile Neuronal Ceroid Lipofuscinosis Molecular Diagnosis

    OpenAIRE

    Liliana Catherine Patiño; Rajani Battu; Oscar Ortega-Recalde; Jeyabalan Nallathambi; Venkata Ramana Anandula; Umashankar Renukaradhya; Paul Laissue

    2014-01-01

    The neuronal ceroid-lipofuscinoses (NCL) is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and...

  17. Crystal Structure and Autoactivation Pathway of the Precursor Form of Human Tripeptidyl-peptidase 1, the Enzyme Deficient in Late Infantile Ceroid Lipofuscinosis* S⃞

    OpenAIRE

    Guhaniyogi, Jayita; Sohar, Istvan; Das, Kalyan; Stock, Ann M.; Lobel, Peter

    2009-01-01

    Late infantile neuronal ceroid lipofuscinosis is a fatal childhood neurological disorder caused by a deficiency in the lysosomal protease tripeptidyl-peptidase 1 (TPP1). TPP1 represents the only known mammalian member of the S53 family of serine proteases, a group characterized by a subtilisin-like fold, a Ser-Glu-Asp catalytic triad, and an acidic pH optimum. TPP1 is synthesized as an inactive proenzyme (pro-TPP1) that is proteolytically processed into the active enzyme after exposure to low...

  18. Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum.

    Science.gov (United States)

    Phillips, Jonathan E; Gomer, Richard H

    2015-02-01

    Neuronal ceroid lipofuscinosis (NCL) is the most common childhood-onset neurodegenerative disease. NCL is inevitably fatal, and there is currently no treatment available. Children with NCL show a progressive decline in movement, vision and mental abilities, and an accumulation of autofluorescent deposits in neurons and other cell types. Late-infantile NCL is caused by mutations in the lysosomal protease tripeptidyl peptidase 1 (TPP1). TPP1 cleaves tripeptides from the N-terminus of proteins in vitro, but little is known about the physiological function of TPP1. TPP1 shows wide conservation in vertebrates but it is not found in Drosophila, Caenorhabditis elegans or Saccharomyces cerevisiae. Here, we characterize ddTpp1, a TPP1 ortholog present in the social amoeba Dictyostelium discoideum. Lysates from cells lacking ddTpp1 show a reduced but not abolished ability to cleave a TPP1 substrate, suggesting that other Dictyostelium enzymes can perform this cleavage. ddTpp1 and human TPP1 localize to the lysosome in Dictyostelium, indicating conserved function and trafficking. Cells that lack ddTpp1 show precocious multicellular development and a reduced ability to form spores during development. When cultured in autophagy-stimulating conditions, cells lacking ddTpp1 rapidly decrease in size and are less viable than wild-type cells, suggesting that one function of ddTpp1 could be to limit autophagy. Cells that lack ddTpp1 exhibit strongly impaired development in the presence of the lysosome-perturbing drug chloroquine, and this phenotype can be suppressed through a secondary mutation in the gene that we name suppressor of tpp1(-) A (stpA), which encodes a protein with some similarity to mammalian oxysterol-binding proteins (OSBPs). Taken together, these results suggest that targeting specific proteins could be a viable way to suppress the effects of loss of TPP1 function. PMID:25540127

  19. Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum

    Directory of Open Access Journals (Sweden)

    Jonathan E. Phillips

    2015-02-01

    Full Text Available Neuronal ceroid lipofuscinosis (NCL is the most common childhood-onset neurodegenerative disease. NCL is inevitably fatal, and there is currently no treatment available. Children with NCL show a progressive decline in movement, vision and mental abilities, and an accumulation of autofluorescent deposits in neurons and other cell types. Late-infantile NCL is caused by mutations in the lysosomal protease tripeptidyl peptidase 1 (TPP1. TPP1 cleaves tripeptides from the N-terminus of proteins in vitro, but little is known about the physiological function of TPP1. TPP1 shows wide conservation in vertebrates but it is not found in Drosophila, Caenorhabditis elegans or Saccharomyces cerevisiae. Here, we characterize ddTpp1, a TPP1 ortholog present in the social amoeba Dictyostelium discoideum. Lysates from cells lacking ddTpp1 show a reduced but not abolished ability to cleave a TPP1 substrate, suggesting that other Dictyostelium enzymes can perform this cleavage. ddTpp1 and human TPP1 localize to the lysosome in Dictyostelium, indicating conserved function and trafficking. Cells that lack ddTpp1 show precocious multicellular development and a reduced ability to form spores during development. When cultured in autophagy-stimulating conditions, cells lacking ddTpp1 rapidly decrease in size and are less viable than wild-type cells, suggesting that one function of ddTpp1 could be to limit autophagy. Cells that lack ddTpp1 exhibit strongly impaired development in the presence of the lysosome-perturbing drug chloroquine, and this phenotype can be suppressed through a secondary mutation in the gene that we name suppressor of tpp1− A (stpA, which encodes a protein with some similarity to mammalian oxysterol-binding proteins (OSBPs. Taken together, these results suggest that targeting specific proteins could be a viable way to suppress the effects of loss of TPP1 function.

  20. A novel mutation in the MFSD8 gene in late infantile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Stogmann, E; El Tawil, S; Wagenstaller, J; Gaber, A; Edris, S; Abdelhady, A; Assem-Hilger, E; Leutmezer, F; Bonelli, S; Baumgartner, C; Zimprich, F; Strom, T M; Zimprich, A

    2009-02-01

    Neuronal ceroid lipofuscinoses (NCL) are lysosomal storage disorders and constitute the most common group of progressive neurodegenerative diseases in childhood. Most NCLs are inherited in a recessive manner and are clinically characterised by a variable age at onset, epileptic seizures, psychomotor decline, visual impairment and premature death. To date, eight causative genes have been identified to underlie various clinical forms of NCL. We performed a genome-wide linkage analysis followed by sequencing the recently described NCL gene MFSD8 in three affected and three unaffected members of a consanguineous Egyptian family with an autosomal recessively inherited progressive neurodegenerative disorder. The clinical picture of the patients was compatible with a late infantile NCL (LINCL); however, impairment of the visual system was not a cardinal symptom in the respective family. By linkage analysis, we identified two putative loci on chromosome 1p36.11-p35.1 and 4q28.1-q28.2. The latter locus (4q28.1-q28.2) contained the MFSD8 gene, comprising a novel homozygous missense mutation in exon 5 (c.362a>g /p.Tyr121Cys), which segregated with the disease in the three affected sibs. We describe a novel mutation in the previously identified MFSD8 gene in a family with a common phenotype of LINCL, but no clinical report of vision loss. Our results enlarge the mutational and perhaps the nosological spectrum of one of the recently identified subtypes of NCL, called CLN7. PMID:18850119

  1. Exome sequencing is an efficient tool for variant late-infantile neuronal ceroid lipofuscinosis molecular diagnosis.

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    Liliana Catherine Patiño

    Full Text Available The neuronal ceroid-lipofuscinoses (NCL is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14 have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8 and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg and c.1361T>C (p.Met454Thr MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease.

  2. Sustained Neural Stem Cell-Based Intraocular Delivery of CNTF Attenuates Photoreceptor Loss in the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis.

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    Wanda Jankowiak

    Full Text Available A sustained intraocular administration of neurotrophic factors is among the strategies aimed at establishing treatments for currently untreatable degenerative retinal disorders. In the present study we have analyzed the neuroprotective effects of a continuous neural stem (NS cell-based intraocular delivery of ciliary neurotrophic factor (CNTF on photoreceptor cells in the nclf mouse, an animal model of the neurodegenerative lysosomal storage disorder variant late infantile neuronal ceroid lipofuscinosis (vLINCL. To this aim, we genetically modified adherently cultivated NS cells with a polycistronic lentiviral vector encoding a secretable variant of CNTF together with a Venus reporter gene (CNTF-NS cells. NS cells for control experiments (control-NS cells were modified with a vector encoding the reporter gene tdTomato. Clonal CNTF-NS and control-NS cell lines were established using fluorescent activated cell sorting and intravitreally grafted into 14 days old nclf mice at the onset of retinal degeneration. The grafted cells preferentially differentiated into astrocytes that were attached to the posterior side of the lenses and the vitreal side of the retinas and stably expressed the transgenes for at least six weeks, the latest post-transplantation time point analyzed. Integration of donor cells into host retinas, ongoing proliferation of grafted cells or adverse effects of the donor cells on the morphology of the host eyes were not observed. Quantitative analyses of host retinas two, four and six weeks after cell transplantation revealed the presence of significantly more photoreceptor cells in eyes with grafted CNTF-NS cells than in eyes with grafted control-NS cells. This is the first demonstration that a continuous intraocular administration of a neurotrophic factor attenuates retinal degeneration in an animal model of neuronal ceroid lipofuscinosis.

  3. Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan.

    Science.gov (United States)

    Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Kawahara, Natsuko; Hayashi, Daisuke; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

    2011-11-01

    Neuronal ceroid lipofuscinosis (NCL) constitutes a group of recessively inherited lysosomal storage diseases that primarily affect neuronal cells. Such diseases share certain clinical and pathologic features in human beings and animals. Neuronal ceroid lipofuscinosis in Border Collie dogs was first detected in Australia in the 1980s, and the pathogenic mutation was shown to be a nonsense mutation (c.619C>T) in exon 4 in canine CLN5 gene. In the present study, novel rapid genotyping assays including polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR primer-induced restriction analysis, mutagenically separated PCR, and real-time PCR with TaqMan minor groove binder probes, were developed. The utility of microchip electrophoresis was also evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies in Japan using these assays to determine the current allele frequency in Japan, providing information to control and prevent this disease in the next stage. All assays developed in the current study are available to discriminate these genotypes, and microchip electrophoresis showed a timesaving advantage over agarose gel electrophoresis. Of all assays, real-time PCR was the most suitable for large-scale examination because of its high throughput. The genotyping survey demonstrated that the carrier frequency was 8.1%. This finding suggested that the mutant allele frequency of NCL in Border Collies is high enough in Japan that measures to control and prevent the disease would be warranted. The genotyping assays developed in the present study could contribute to the prevention of NCL in Border Collies. PMID:22362793

  4. Large alterations in ganglioside and neutral glycosphingolipid patterns in brains from cases with infantile neuronal ceroid lipofuscinosis/polyunsaturated fatty acid lipidosis.

    Science.gov (United States)

    Svennerholm, L; Fredman, P; Jungbjer, B; Månsson, J E; Rynmark, B M; Boström, K; Hagberg, B; Norén, L; Santavuori, P

    1987-12-01

    Lipid composition was studied on cerebral tissue from nine children who had died of a progressive encephalopathy called the infantile form of neuronal ceroid lipofuscinosis (INCL) or polyunsaturated fatty acid lipidosis (PFAL). In the terminal stage of the disease, the concentrations of all lipid classes were found to be significantly reduced in the cerebral and cerebellar cortex and white matter. The concentration of gangliosides of the cerebral cortex was 15% and that of cerebrosides (galactosylceramide) in white matter 0.2-5% of the normal values for the children's ages. The reduction of gangliosides mainly affected those of the gangliotetraose series, particularly GD1a. The fatty acids of the linolenic acid series were strongly reduced in ethanolamine and serine phosphoglycerides. A very large increase up to 100-fold of oligoglycosphingolipids of the globo series and two fucose-containing lipids of the neolacto series was found in the forebrain of the three advanced cases examined. The brain tissue also contained very high concentrations of mono-, di-, and trisialogangliosides of the lacto and neolacto series, gangliosides with type 1 chain dominating. The structures of the gangliosides were tentatively identified by gas chromatography-mass spectrometry and monoclonal antibodies with carefully determined epitope specificity. The gangliosides and neutral glycosphingolipids had very similar fatty acid composition, consisting of about 40% stearic acid and 40% C24-acids. PMID:3681296

  5. Parent-reported benefits of flupirtine in juvenile neuronal ceroid lipofuscinosis (Batten disease; CLN3) are not supported by quantitative data.

    Science.gov (United States)

    Cialone, Jennifer; Augustine, Erika F; Newhouse, Nicole; Adams, Heather; Vierhile, Amy; Marshall, Frederick J; de Blieck, Elisabeth A; Kwon, Jennifer; Rothberg, Paul G; Mink, Jonathan W

    2011-10-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3 disease; Batten disease) is an autosomal recessive neurodegenerative disease of childhood that typically presents at school age with vision loss followed by progressive cognitive decline, motor dysfunction, seizures, and behavior problems. No therapy has been shown to slow the progression of disease in JNCL patients, and all current treatments are symptomatic. Flupirtine has been shown in vitro to reduce apoptosis in CLN3 lymphocytes. Based on that preclinical study, several children with JNCL were given flupirtine by their parents. The purpose of this study was to determine if there was evidence of attenuated disease progression in any JNCL symptom domain. We administered a survey to parents of JNCL children to qualitatively assess flupirtine efficacy. We used the Unified Batten Disease Rating Scale (UBDRS) to determine specific aspects of disease progression and investigated three age-related factors: loss of independent ambulation, loss of intelligible speech, and loss of ability to perform independent activities of daily living. The median scores for the UBDRS physical, behavior, and capability subscales were determined in flupirtine-exposed subjects and compared to age-, sex-, and genotype-matched subjects who had never taken flupirtine. Twenty-one percent of survey responders reported administering flupirtine to their JNCL child, and 56% of these families perceived beneficial changes that they attributed to flupirtine. However, our quantitative, prospectively obtained data did not show any change in JNCL disease progression that could be attributed to flupirtine. This study highlights the need for prospective experimental therapeutic research. PMID:21556831

  6. Portuguese family with the co-occurrence of frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation.

    Science.gov (United States)

    Almeida, Maria R; Macário, Maria C; Ramos, Lina; Baldeiras, Inês; Ribeiro, Maria H; Santana, Isabel

    2016-05-01

    We and others have reported heterozygous progranulin mutations as an important cause of frontotemporal lobar degeneration (FTLD). It has been identified a complete progranulin deficiency because of a homozygous mutation in a sibling pair with neuronal ceroid lipofuscinosis (NCL). Here, we describe the first case of NCL caused by a homozygous progranulin mutation segregating in a family with neuropathological confirmed FTLD. In this FTLD-NCL family, we detail the clinical phenotype, neuropsychological evaluation and imaging data of our proband harboring a homozygous mutation, c.900_901dupGT, with serum progranulin level (retinal dystrophy diagnosis and magnetic resonance imaging showed severe global cerebellar atrophy. In contrast, heterozygous relatives presented behavioral variant of frontotemporal dementia (FTD) and some also developed extrapyramidal features compatible with corticobasal syndrome. Our findings suggest the importance of assessing serum progranulin levels in suspected recessive adult-onset NCL cases. Overall, a more holistic neurologic intervention is needed to guarantee a proper genetic counseling in cases like the present family where two distinct phenotypes are generated according to the individuals' mutation state. PMID:27021778

  7. Analysis of phospholipid molecular species in brains from patients with infantile and juvenile neuronal-ceroid lipofuscinosis using liquid chromatography-electrospray ionization mass spectrometry.

    Science.gov (United States)

    Käkelä, Reijo; Somerharju, Pentti; Tyynelä, Jaana

    2003-03-01

    Phospholipids (PL) in cerebral cortex from patients with infantile (INCL or CLN1) and juvenile (JNCL or CLN3) forms of neuronal ceroid-lipofuscinosis (NCL) and controls were analysed by normal phase HPLC and on-line electrospray ionization ion-trap mass spectrometric detection (LC-ESI-MS). The method provided quantitative data on numerous molecular species of different PL classes, which are not achieved by using the conventional chromatographic methods. Compared with the controls, the INCL brains contained proportionally more phosphatidylcholine (PC), and less phosphatidylethanolamine (PE) and phosphatidylserine (PS). Different molecular species of PC, PE, PS, phosphatidylinositol and sphingomyelin were quantified using multiple internal PL standards that differed in fatty acyl chain length and thus allowed correction for chain length dependency of instrument response. In INCL cortex, which had lost 65% of the normal PL content, the proportions of polyunsaturated molecular species, especially the PS and PE that contained docosahexaenoic acid (22:6n-3), were dramatically decreased. The membranes may have adapted to this alteration by increasing the proportions of PL molecules substituted with monounsaturated and short-chain fatty acids. Lysobisphosphatidic acid was highly elevated in the INCL brain and consisted mostly of polyunsaturated species. It is possible that changes in the composition of PL membranes accelerate progression of INCL by altering signalling and membrane trafficking in neurons. PMID:12603829

  8. Progressive retinal degeneration and glial activation in the CLN6 (nclf mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation.

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    Myriam Mirza

    Full Text Available Neuronal ceroid lipofuscinosis (NCL is a group of neurodegenerative lysosomal storage disorders characterized by vision loss, mental and motor deficits, and spontaneous seizures. Neuropathological analyses of autopsy material from NCL patients and animal models revealed brain atrophy closely associated with glial activity. Earlier reports also noticed loss of retinal cells and reactive gliosis in some forms of NCL. To study this phenomenon in detail, we analyzed the ocular phenotype of CLN6 (nclf mice, an established mouse model for variant-late infantile NCL. Retinal morphometry, immunohistochemistry, optokinetic tracking, electroretinography, and mRNA expression were used to characterize retinal morphology and function as well as the responses of Müller cells and microglia. Our histological data showed a severe and progressive degeneration in the CLN6 (nclf retina co-inciding with reactive Müller glia. Furthermore, a prominent phenotypic transformation of ramified microglia to phagocytic, bloated, and mislocalized microglial cells was identified in CLN6 (nclf retinas. These events overlapped with a rapid loss of visual perception and retinal function. Based on the strong microglia reactivity we hypothesized that dietary supplementation with immuno-regulatory compounds, curcumin and docosahexaenoic acid (DHA, could ameliorate microgliosis and reduce retinal degeneration. Our analyses showed that treatment of three-week-old CLN6 (nclf mice with either 5% DHA or 0.6% curcumin for 30 weeks resulted in a reduced number of amoeboid reactive microglia and partially improved retinal function. DHA-treatment also improved the morphology of CLN6 (nclf retinas with a preserved thickness of the photoreceptor layer in most regions of the retina. Our results suggest that microglial reactivity closely accompanies disease progression in the CLN6 (nclf retina and both processes can be attenuated with dietary supplemented immuno-modulating compounds.

  9. An atypical case of neuronal ceroid lipofuscinosis with co-inheritance of a variably penetrant POLG1 mutation

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    Staropoli John F

    2012-06-01

    Full Text Available Abstract Background The neuronal ceroid lipofuscinoses (NCLs, or Batten disease comprise the most common Mendelian form of childhood-onset neurodegeneration, but the functions of the known underlying gene products remain poorly understood. The clinical heterogeneity of these disorders may shed light on genetic interactors that modify disease onset and progression. Case presentation We describe a proband with congenital hypotonia and an atypical form of infantile-onset, biopsy-proven NCL. Pathologic and molecular work-up of this patient identified CLN5 mutations as well as a mutation―previously described as incompletely penetrant or a variant of unknown significance―in POLG1, a nuclear gene essential for maintenance of mitochondrial DNA (mtDNA copy number. The congenital presentation of this patient is far earlier than that described for either CLN5 patients or affected carriers of the POLG1 variant (c.1550 G > T, p.Gly517Val. Assessment of relative mtDNA copy number and mitochondrial membrane potential in the proband and control subjects suggested a pathogenic effect of the POLG1 change as well as a possible functional interaction with CLN5 mutations. Conclusions These findings suggest that an incompletely penetrant variant in POLG1 may modify the clinical phenotype in a case of CLN5 and are consistent with emerging evidence of interactions between NCL-related genes and mitochondrial physiology.

  10. Association between CLN3 (Neuronal Ceroid Lipofuscinosis, CLN3 type gene expression and clinical characteristics of breast cancer patients

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    Rose-Mary eBoustany

    2015-10-01

    Full Text Available Breast cancer is the most common cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. CLN3 protein (CLN3p, deficient in neurodegenerative CLN3 disease is anti-apoptotic, and defects in the CLN3 gene cause accelerated apoptosis of neurons in CLN3 disease and upregulation of ceramide. Dysregulated apoptotic pathways are often implicated in the development of the oncogenic phenotype. Predictably, CLN3 mRNA expression and CLN3 protein were upregulated in a number of human and murine breast cancer cell lines. Here, we determine CLN3 expression in non-tumor vs. tumor samples from fresh and formalin-fixed/paraffin-embedded (FFPE breast tissue and analyze the association between CLN3 overexpression and different clinicopathological characteristics of breast cancer patients. Additionally, gene expression of 28 enzymes involved in sphingolipid metabolism was determined. CLN3 mRNA is overexpressed in tumor vs. non-tumor breast tissue from FFPE and fresh samples, as well as in mouse MCF7 breast cancer compared to MCF10A normal cells. Of the clinicopathological characteristics of tumor grade, age, menopause status, estrogen receptor (ER, progesterone receptor (PR, and human epidermal growth factor receptor 2 (HER2, only absence of HER2 expression correlated with CLN3 overexpression. Sphingolipid genes for ceramide synthases 2 and 6 (CerS2; CerS6, delta(4-desaturase sphingolipid 2 (DEGS2 and acidic sphingomyelinase (SMPD1 displayed higher expression levels in breast cancer vs. control tissue, whereas, ceramide galactosyltransferase (UGT8 was underexpressed in breast cancer samples. CLN3 may be a novel molecular target for cancer drug discovery with the goal of modulation of ceramide pathways.

  11. Computed tomography of rambouillet sheep affected with neuronal ceroid lepofuscinosis

    International Nuclear Information System (INIS)

    Computed tomography (CT) was performed on 3 normal Rambouillet sheep and 6 Rambouillet sheep affected with neuronal ceroid lipofuscinosis. Characteristic lesions seen in the brain of affected sheep included dramatically enlarged lateral ventricles and reduced cerebral thickness. The lesions were seen in sheep as young as 4 months of age. Antemortem CT observations correlated well with postmortem findings in this model of Neuronal Ceroid Lipofuscinosis

  12. Genetics Home Reference: infantile neuronal ceroid lipofuscinosis

    Science.gov (United States)

    ... Beginning in infancy, children with this condition have intellectual and motor disability, rarely developing the ability to speak or walk. Affected children often have muscle twitches (myoclonus), recurrent seizures (epilepsy), ...

  13. Genetics Home Reference: congenital neuronal ceroid lipofuscinosis

    Science.gov (United States)

    ... an inherited disorder that primarily affects the nervous system. Soon after birth, affected infants develop muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that ...

  14. Clinico-investigative profile of infantile and late-infantile neuronal ceroid lipofuscinoses

    Directory of Open Access Journals (Sweden)

    Mahesh Kamate

    2012-01-01

    Full Text Available Neuronal ceroid lipofuscinosis is a group of progressive neurodegenerative disorders characterized by accumulation of ceroid lipopigment in lysosomes in neurons and other cell types. This study is a retrospective review of charts of patients with a diagnosis of infantile and late-infantile neuronal ceroid lipofuscinosis seen between January 2009 and December 2011. Of the 16 patients, 5 had infantile type and 11 had late-infantile neuronal ceroid lipofuscinosis. Diagnosis was confirmed by appropriate enzyme assay. Clinical presentation was quite varied. Common presenting features included refractory seizures, developmental delay/regression, and abnormal movements. Visual failure was not common in the present case series, and novel neuroimaging finding in the form of isolated dentate nucleus hyperintensities were noted. During follow-up, all patients had a progressive downhill course and one patient died. Prenatal diagnosis could be offered to one family. This study suggests that infantile and late-infantile neuronal ceroid lipofuscinosis is not uncommon in this region of the country and the phenotype may be different.

  15. 神经元蜡样质脂褐质沉积病(NCL)的基因型与表型相关性研究%Genotype-phenotype analyses of classic neuronal ceroid lipofuscinosis (NCLs): genetic predictions from clinical and pathological findings

    Institute of Scientific and Technical Information of China (English)

    Weina JU; W. Ted BROWN; Nanbert ZHONG; Anetta WRONSKA; Dorota N. MOROZIEWICZ; Rocksheng ZHONG; Natalia WISNIEWSKI; Anna JURKIEWICZ; Michael FIORY; Krystyna E. WISNIEWSKI; Lance JOHNSTON

    2006-01-01

    Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles. Results: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type EM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) cases.Conclusion:Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.

  16. Neuronal ceroid-lipofuscinosis, a type of amaurotic family idiocy: clinical and pathological study of four cases Ceróide-lipofuscinose neuronal, um tipo de idiotia amaurótica familiar: estudo clínico-patológico de quatro casos

    Directory of Open Access Journals (Sweden)

    Luciano de Souza Queiroz

    1974-03-01

    Full Text Available Neuronal ceroid-lipofuscinosis (NCL is a recent term, proposed for acurate designation of the late-onset types of Amaurotic Family Idiocy (AFI. Histopathology shows ubiquitous intraneuronal accumulation of lipopigments, being the most important factor for characterization of the entity at present time. Biochemical changes and pathogenesis are obscure. NCL is in contrast to the infantile type of AFI (Tay-Sachs disease, in which intraneuronal accumulation of gangliosides (sphingolipids is due to the well known deficiency of a lysosomal enzyme. The authors report on four cases of NCL, two brothers of the late infantile (Jansky-Bielschowsky type and a brother and a sister of the juvenile (Spielmeyer-Sjögren type. One autopsy and three cortical biopsies revealed moderate to severe distention of the neurons by lipopigment, with nerve cell loss, gliosis and cerebral atrophy. Lipopigment was also increased in liver, heart and spleen. The patients were the first in Brazilian literature in whom the storage material was identified as lipopigment by histochemical methods. A brief summary of the clinical features of NCL is presented, and relevant problems are discussed, concerning interpretation of the nature of the storage material, and significance of the disease for gerontological research.Estudos histoquímicos, bioquímicos e ultraestruturais permitiram recentemente distinguir dois tipos de entidades nosológicas dentre as doenças conhecidas como "Idiotia amaurótica familiar" (IAF. O primeiro, que inclue a doença de Tay-Sachs, ou tipo infantil de IAF, é constituido por doenças de armazenamento de gangliósides. Sua patogenia é conhecida, baseando-se em deficiências de enzimas lisossômicos. O segundo grupo, cuja patogenia é desconhecida, foi recentemente designado "Ceróide-lipofuscinose neuronal" (CLN por Zeman e colaboradores. Corresponde aos tipos infantil tardio, juvenil e adulto de IAF, caracterizando-se histopatologicamente pelo ac

  17. The Neuronal Ceroid-Lipofuscinoses

    Science.gov (United States)

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  18. A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

    Energy Technology Data Exchange (ETDEWEB)

    Salek, Reza M.; Pears, Michael R. [University of Cambridge, Department of Biochemistry and Cambridge Systems Biology Centre (United Kingdom); Cooper, Jonathan D. [King' s College London, Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry (United Kingdom); Mitchison, Hannah M. [Royal Free and University College Medical School, Department of Paediatrics and Child Health (United Kingdom); Pearce, David A. [Sanford School of Medicine of the University of South Dakota, Department of Pediatrics (United States); Mortishire-Smith, Russell J. [Johnson and Johnson PR and D (Belgium); Griffin, Julian L., E-mail: jlg40@mole.bio.cam.ac.uk [University of Cambridge, Department of Biochemistry and the Cambridge Systems Biology Centre (United Kingdom)

    2011-04-15

    The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in {gamma}-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

  19. Lacritin and other autophagy associated proteins in ocular surface health.

    Science.gov (United States)

    Karnati, Roy; Talla, Venu; Peterson, Katherine; Laurie, Gordon W

    2016-03-01

    Advantage may be taken of macroautophagy ('autophagy') to promote ocular health. Autophagy continually captures aged or damaged cellular material for lysosomal degradation and recyling. When autophagic flux is chronically elevated, or alternatively deficient, health suffers. Chronic elevation of flux and stress are the consequence of inflammatory cytokines or of dry eye tears but not normal tears invitro. Exogenous tear protein lacritin transiently accelerates flux to restore homeostasis invitro and corneal health invivo, and yet the monomeric active form of lacritin appears to be selectively deficient in dry eye. Tissue transglutaminase-dependent cross-linking of monomer decreases monomer quantity and monomer affinity for coreceptor syndecan-1 thereby abrogating activity. Tissue transglutaminase is elevated in dry eye. Mutation of arylsulfatase A, arylsulfatase B, ceroid-lipofuscinosis neuronal 3, mucolipin, or Niemann-Pick disease type C1 respectively underlie several diseases of apparently insufficient autophagic flux that affect the eye, including: metachromatic leukodystrophy, mucopolysaccharidosis type VI, juvenile-onset Batten disease, mucolipidosis IV, and Niemann-Pick type C associated with myelin sheath destruction of corneal sensory and ciliary nerves and of the optic nerve; corneal clouding, ocular hypertension, glaucoma and optic nerve atrophy; accumulation of 'ceroid-lipofuscin' in surface conjunctival cells, and in ganglion and neuronal cells; decreased visual acuity and retinal dystrophy; and neurodegeneration. For some, enzyme or gene replacement, or substrate reduction, therapy is proving to be successful. Here we discuss examples of restoring ocular surface homeostasis through alteration of autophagy, with particular attention to lacritin. PMID:26318608

  20. Classification and Natural History of the Neuronal Ceroid Lipofuscinoses

    OpenAIRE

    Mink, Jonathan W.; Augustine, Erika F.; ADAMS, HEATHER R; Marshall, Frederick J.; Kwon, Jennifer M.

    2013-01-01

    The neuronal ceroid lipofuscinoses represent a group of disorders characterized by neurodegeneration and intracellular accumulation of an auto-fluorescent lipopigment (ceroid lipofuscin). Together, they represent the most prevalent class of childhood neurodegenerative disease. The neuronal ceroid lipofuscinoses encompass several distinct biological entities that vary in age of onset, specific neurological phenotype, and rate of progression. In this review, we describe 9 major forms and presen...

  1. Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis

    Directory of Open Access Journals (Sweden)

    Cattaneo Elena

    2004-12-01

    Full Text Available Abstract Background JNCL is a recessively inherited, childhood-onset neurodegenerative disease most-commonly caused by a ~1 kb CLN3 mutation. The resulting loss of battenin activity leads to deposition of mitochondrial ATP synthase, subunit c and a specific loss of CNS neurons. We previously generated Cln3Δex7/8 knock-in mice, which replicate the common JNCL mutation, express mutant battenin and display JNCL-like pathology. Results To elucidate the consequences of the common JNCL mutation in neuronal cells, we used P4 knock-in mouse cerebella to establish conditionally immortalized CbCln3 wild-type, heterozygous, and homozygous neuronal precursor cell lines, which can be differentiated into MAP-2 and NeuN-positive, neuron-like cells. Homozygous CbCln3Δex7/8 precursor cells express low levels of mutant battenin and, when aged at confluency, accumulate ATPase subunit c. Recessive phenotypes are also observed at sub-confluent growth; cathepsin D transport and processing are altered, although enzyme activity is not significantly affected, lysosomal size and distribution are altered, and endocytosis is reduced. In addition, mitochondria are abnormally elongated, cellular ATP levels are decreased, and survival following oxidative stress is reduced. Conclusions These findings reveal that battenin is required for intracellular membrane trafficking and mitochondrial function. Moreover, these deficiencies are likely to be early events in the JNCL disease process and may particularly impact neuronal survival.

  2. Osmotic stress changes the expression and subcellular localization of the Batten disease protein CLN3.

    Directory of Open Access Journals (Sweden)

    Amanda Getty

    Full Text Available Juvenile CLN3 disease (formerly known as juvenile neuronal ceroid lipofuscinosis is a fatal childhood neurodegenerative disorder caused by mutations in the CLN3 gene. CLN3 encodes a putative lysosomal transmembrane protein with unknown function. Previous cell culture studies using CLN3-overexpressing vectors and/or anti-CLN3 antibodies with questionable specificity have also localized CLN3 in cellular structures other than lysosomes. Osmoregulation of the mouse Cln3 mRNA level in kidney cells was recently reported. To clarify the subcellular localization of the CLN3 protein and to investigate if human CLN3 expression and localization is affected by osmotic changes we generated a stably transfected BHK (baby hamster kidney cell line that expresses a moderate level of myc-tagged human CLN3 under the control of the human ubiquitin C promoter. Hyperosmolarity (800 mOsm, achieved by either NaCl/urea or sucrose, dramatically increased the mRNA and protein levels of CLN3 as determined by quantitative real-time PCR and Western blotting. Under isotonic conditions (300 mOsm, human CLN3 was found in a punctate vesicular pattern surrounding the nucleus with prominent Golgi and lysosomal localizations. CLN3-positive early endosomes, late endosomes and cholesterol/sphingolipid-enriched plasma membrane microdomain caveolae were also observed. Increasing the osmolarity of the culture medium to 800 mOsm extended CLN3 distribution away from the perinuclear region and enhanced the lysosomal localization of CLN3. Our results reveal that CLN3 has multiple subcellular localizations within the cell, which, together with its expression, prominently change following osmotic stress. These data suggest that CLN3 is involved in the response and adaptation to cellular stress.

  3. In a model of Batten disease, palmitoyl protein thioesterase-1 deficiency is associated with brown adipose tissue and thermoregulation abnormalities.

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    Alfia Khaibullina

    Full Text Available Infantile neuronal ceroid lipofuscinosis (INCL is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1. We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1α and uncoupling protein 1 (Ucp-1 in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1α and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of

  4. NCL Disorders: Frequent Causes of Childhood Dementia

    Directory of Open Access Journals (Sweden)

    Angela SCHULZ

    2013-02-01

    protein CLN5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in Asian sibship. Hum Mutat2009;30:E651-61.Kousi M Lehesjoki AE, Mole SE. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat 2011;33:42-63.Jalanko A, Braulke T. Neuronal ceroid lipofuscinoses. Biochim Biophys Acta 2009;1793:697-709.Arsov T, Smith KR, Damiano J, Franceschetti S, Canafoglia L, Bromhead CJ, et al. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet 2011;88:566-73.Smith KR, Damiano J, Franceschetti S, Carpenter S, Canafoglia L, Morbin M, et al. Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet 2012;90:1102-7.Bras J, Verloes A, Schneider SA, Mole SE, Guerreiro RJ. Mutation of the Parkinsonism Gene ATP13A2 Causes Neuronal Ceroid-Lipofuscinosis. Hum Mol Genet 2012.Noskova L, Stranecky V, Hartmannova H, Pristoupilova A, Baresova V, Ivanek R, et al. Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal- dominant adult-onset neuronal ceroid lipofuscinosis. Am J Hum Genet 2011;89:241-52.Staropoli JF, Karaa A, Lim ET, Kirby A, Elbalalesy N, Romansky SG, et al. A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin- proteasome system. Am J Hum Genet 2012;91:202-8.

  5. Retinaler Phänotyp dreier Mausmodelle für die neuronale Ceroidlipofuszinose

    OpenAIRE

    Dahlmann, Cordula

    2013-01-01

    The aim of this study is the phenotypical characterization of the mouse models for infantile, juvenile and variant late infantile neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinosis is a group of neurodegenerative disorders mostly occuring in childhood. They are characterized by loss of visual function, epilepsia and dementia, disease progression and consecutive early death. The mouse model is of special importance in exploring the functional and pathophysiological basis of the...

  6. Investigation of the Batten Disease protein CLN6.

    OpenAIRE

    Martin, Y

    2006-01-01

    The neuronal ceroid lipofuscinoses (NCLs, Batten Disease) are a group of lysosomal storage disorders caused by mutations in known and unknown proteins with different cellular locations. Mutations in the CLN6 gene cause a type of variant late infantile NCL (vLINCL). The CLN6 protein is located in the ER and how mutations in CLN6 cause accumulation of storage material in the lysosome is unclear. The aims of this thesis were to establish the tools and techniques necessary to analyse the CLN6 pro...

  7. Alteraciones en la degradación intracelular de proteínas y en la endocitosis en las lipofuscinosis ceroideas neuronales infantil tardía y juvenil

    OpenAIRE

    Vidal Donet, José Manuel

    2014-01-01

    Las lipofuscinosis ceroideas neuronales son un grupo heterogéneo de enfermedades neurodegenerativas hereditarias graves que tienen su inicio en la infancia y que se engloban dentro de las enfermedades de almacenamiento lisosomal. Las características clínicas de estas patologías son una disminución de la capacidad mental acompañada de alteraciones motoras, epilepsia y pérdida de visión. Histológicamente las células muestran una acumulación de material autofluorescente (lipofuscina) en el inte...

  8. The paediatric rheumatologist and orphan disease - a story without happy ending.

    Science.gov (United States)

    Roszkiewicz, Justyna; Biernacka-Zielińska, Małgorzata; Smolewska, Elżbieta

    2016-01-01

    Orphan diseases are not a common challenge in the everyday practice of the rheumatologist. Despite their extremely rare occurrence one of the patients under our care developed one of them - neuronal ceroid lipofuscinosis, the most frequent neurodegenerative disease observed in the paediatric population. We report a case of 2-year-old girl diagnosed with oligoarticular form of juvenile idiopathic arthritis treated in our Department with steroids and methotrexate and staying in the stage of disease remission. During routine checkups at Outpatient Clinic we observed progressive deterioration of girls neurological condition resulting in ataxia, gait disturbances with no rheumatological cause behind and speech impairment. The appearance of the symptoms was accompanied by frequent episodes of epileptic seizures, with little clinical improvement on combined antiepileptic treatment. Magnetic resonance imaging that we performed showed a picture highly suggestive of neuronal ceroid lipofuscinosis - atrophy of the patients cerebrum and cerebellum. Genetic testing conducted resulted in the diagnosis of late infantile neuronal ceroid lipofuscinosis (LINCL). PMID:27504025

  9. Distinct early molecular responses to mutations causing vLINCL and JNCL presage ATP synthase subunit C accumulation in cerebellar cells.

    Directory of Open Access Journals (Sweden)

    Yi Cao

    Full Text Available Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL, caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL, caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6(nclf/nclf cerebellar cells and compared them to wild-type and CbCln3(Δex7/8/Δex7/8 cerebellar cells. CbCln6(nclf/nclf cells and CbCln3(Δex7/8/Δex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6(nclf/nclf cells, while fluid-phase endocytosis and LysoTracker® labeled vesicles were decreased in both CbCln6(nclf/nclf and CbCln3(Δex7/8/Δex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3(Δex7/8 and Cln6(nclf mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival.

  10. Neuronal ceroid lipofuscinoses: a clinical and morphological study of 17 patients from Southern Brazil Lipofuscinoses ceróides neuronais: estudo clínico e morfológico de 17 pacientes do Sul do Brasil

    Directory of Open Access Journals (Sweden)

    ANA CRISTINA S PUGA

    2000-09-01

    Full Text Available The neuronal ceroid lipofuscinoses (NCL are a group of inherited progressive neurodegenerative disorders with presentation from infancy to adulthood. Three main childhood forms can be established on the basis of age of onset, clinical course, and ultrastructural morphology: infantile (INCL, late infantile (LINCL, and juvenile (JNCL. Several variant subtypes have been described. Genetic and biochemical analysis are helping to better understand, diagnose and classify these disorders. We report on clinical, neurophysiological, neuroradiological, and morphological data from 17 patients with different forms (infantile, late infantile, and juvenile of neuronal ceroid lipofuscinoses (NCL evaluated at Hospital de Clínicas de Porto Alegre, Southern Brazil, during 6 years (1992-1997. Seven cases were infantile; 5 were late infantile; and 5 were juvenile NCL. Gender ratio was male:female, 11:6. Age at presentation varied from 2-24 months for INCL; 2,5 to 5 years for LINCL ; and 4-10 years for the JNCL cases. Seizures (6 patients and psychomotor retardation (1 patient were the initial symptoms in the INCL group. All the patients in the group of LINCL had the usual findings. JNCL patients manifested different initial symptoms, although tending to follow a similar clinical picture within familial cases. Epidemiological data on the prevalence of NCLs in Brazil are not available, we expect this series of cases to contribute to further research in our population.As lipofuscinoses ceroides neuronais (LCN constituem um grupo de desordens neurodegenerativas, progressivas e de origem genética. O início dos sintomas varia desde a infancia até a vida adulta. Três principais formas infantis são estabelecidas com base na idade de início, evolução clínica e morfologia celular, através de microscopia eletrônica: infantil (LCNI, infantil tardia (LCNIT e juvenil (LCNJ. Vários subtipos têm sido descritos. Investigação genética e bioquímica vem

  11. AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease

    Science.gov (United States)

    Katz, Martin L.; Tecedor, Luis; Chen, Yonghong; Williamson, Baye G.; Lysenko, Elena; Wininger, Fred A.; Young, Whitney M.; Johnson, Gayle C.; Whiting, Rebecca E. H.; Coates, Joan R.; Davidson, Beverly L.

    2016-01-01

    The most common form of the childhood neurodegenerative disease late infantile neuronal ceroid lipofuscinosis (also called Batten disease) is caused by deficiency of the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1) resulting from mutations in the TPP1 gene. We tested whether TPP1 gene transfer to the ependyma, the epithelial lining of the brain ventricular system, in TPP1-deficient dogs would be therapeutically beneficial. A one-time administration of recombinant adeno-associated virus (rAAV) expressing canine TPP1 (rAAV.caTPP1) resulted in high expression of TPP1 predominantly in ependymal cells and secretion of the enzyme into the cerebrospinal fluid leading to clinical benefit. Diseased dogs treated with rAAV.caTPP1 showed delays in onset of clinical signs and disease progression, protection from cognitive decline, and extension of life span. By immunostaining and enzyme assay, recombinant protein was evident throughout the brain and spinal cord, with correction of the neuropathology characteristic of the disease. This study in a naturally occurring canine model of TPP1 deficiency highlights the utility of AAV transduction of ventricular lining cells to accomplish stable secretion of recombinant protein for broad distribution in the central nervous system and therapeutic benefit. PMID:26560358

  12. δ-Tocopherol reduces lipid accumulation in Niemann-Pick type C1 and Wolman cholesterol storage disorders.

    Science.gov (United States)

    Xu, Miao; Liu, Ke; Swaroop, Manju; Porter, Forbes D; Sidhu, Rohini; Firnkes, Sally; Finkes, Sally; Ory, Daniel S; Marugan, Juan J; Xiao, Jingbo; Southall, Noel; Pavan, William J; Davidson, Cristin; Walkley, Steven U; Remaley, Alan T; Baxa, Ulrich; Sun, Wei; McKew, John C; Austin, Christopher P; Zheng, Wei

    2012-11-16

    Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a δ-tocopherol-induced intracellular Ca(2+) response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that δ-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases. PMID:23035117

  13. Fibrates inhibit the apoptosis of Batten disease lymphoblast cells via autophagy recovery and regulation of mitochondrial membrane potential.

    Science.gov (United States)

    Hong, Minho; Song, Ki Duk; Lee, Hak-Kyo; Yi, SunShin; Lee, Yong Seok; Heo, Tae-Hwe; Jun, Hyun Sik; Kim, Sung-Jo

    2016-03-01

    Batten disease (BD; also known as juvenile neuronal ceroid lipofuscinosis) is a genetic disorder inherited as an autosomal recessive trait and is characterized by blindness, seizures, cognitive decline, and early death resulting from the inherited mutation of the CLN3 gene. Mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, disrupted autophagy, and enhanced apoptosis have been suggested to play a role in BD pathogenesis. Fibrates, a class of lipid-lowering drugs that induce peroxisome proliferator-activated receptor-α (PPAR-α) activation, are the most commonly used PPAR agonists. Assuming that fibrates have a neuroprotective effect, we studied the effects of fibrates, fenofibrate, bezafibrate, and gemfibrozil on apoptosis, depolarization of mitochondrial membrane, and defective autophagy in BD lymphoblast cells. The viability of fibrate-treated BD lymphoblast cells increased to levels of normal lymphoblast cells. In addition, treatment with fibrates inhibited depolarization of mitochondrial membrane potential in BD lymphoblast cells. Defective autophagy in BD lymphoblast cells was normalized when treated with fibrates as indicated by increased acridine orange staining. The recovery of autophagy in BD lymphoblast cells is most likely attributed to the upregulation of autophagy proteins, lysosomal-associated membrane protein 1 (LAMP1), and LC3 I/II, after treatment with fibrates. This study therefore suggests that fibrates may have a therapeutic potential against BD. PMID:26659390

  14. Positional cloning of disease genes on chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Doggett, N. [Los Alamos National Lab., NM (United States); Bruening, M. [Leiden Univ. (Netherlands); Callen, D. [Adelaide Women`s and Children`s Hospital, North Adelaide, South Australia (Australia); Gardiner, M. [University Coll., London (United Kingdom); Lerner, T. [Massachusetts General Hospital, Boston, MA (United States)

    1996-04-01

    The project seeks to elucidate the molecular basis of an important genetic disease (Batten`s disease) by molecular cloning of the affected gene by utilizing an overlapping clone map of chromosome 16. Batten disease (also known as juvenile neuronal ceroid lipofuscinosis) is a recessively inherited neurodegenerative disorder of childhood characterized by progressive loss of vision, seizures, and psychomoter disturbances. The Batten disease gene was genetically mapped to the chromosome region 16p 12.1 in close linkage with the genetic markers D16S299 and D16S298. Exon amplification of a cosmid containing D16S298 yielded a candidate gene that was disrupted by a 1 kb genomic deletion in all patients containing the most common haplotype for the disease. Two separate deletions and a point mutation altering a splice site in three unrelated families have confirmed the gene as the Batten disease gene. The disease gene encodes a novel 438 amino acid membrane binding protein of unknown function.

  15. A central role for TOR signalling in a yeast model for juvenile CLN3 disease

    Directory of Open Access Journals (Sweden)

    Michael E. Bond

    2015-11-01

    Full Text Available Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. We study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs or Batten disease in the fission yeast Schizosaccharomyces pombe. A global screen for genetic interactions with btn1 highlighted a conserved key signalling hub in which multiple components functionally relate to this conserved disease gene. This signalling hub includes two major mitogen-activated protein kinase (MAPK cascades, and centers on the Tor kinase complexes TORC1 and TORC2. We confirmed that yeast cells modelling CLN3 disease exhibit features consistent with dysfunction in the TORC pathways, and showed that modulating TORC function leads to a comprehensive rescue of defects in this yeast disease model. The same pathways may be novel targets in the development of therapies for the NCLs and related diseases.

  16. Large-scale phenotyping of an accurate genetic mouse model of JNCL identifies novel early pathology outside the central nervous system.

    OpenAIRE

    Staropoli, John F.; Haliw, Larissa; Biswas, Sunita; Garrett, Lillian; Hölter, Sabine M.; Becker, Lore; Skosyrski, Sergej; Da Silva-Buttkus, Patricia; Calzada-Wack, Julia; Neff, Frauke; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Adler, Thure; Puk, Oliver

    2012-01-01

    Cln3(Δex7/8) mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3(Δex7/8) mice. Homozygous Cln3(Δex7/8) mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10-14 wee...

  17. Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System

    OpenAIRE

    Staropoli, John F.; Haliw, Larissa; Biswas, Sunita; Garrett, Lillian; Hölter, Sabine M.; Becker, Lore; Skosyrski, Sergej; Da Silva-Buttkus, Patricia; Calzada-Wack, Julia; Neff, Frauke; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Adler, Thure; Puk, Oliver

    2012-01-01

    Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of ...

  18. Protein Foods

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Protein Foods Foods high in protein such as fish, ... the vegetarian proteins, whether they have carbohydrate. Best Protein Choices The best choices are: Plant-based proteins ...

  19. Protein-protein interactions

    DEFF Research Database (Denmark)

    Byron, Olwyn; Vestergaard, Bente

    2015-01-01

    Responsive formation of protein:protein interaction (PPI) upon diverse stimuli is a fundament of cellular function. As a consequence, PPIs are complex, adaptive entities, and exist in structurally heterogeneous interplays defined by the energetic states of the free and complexed protomers. The...

  20. : Protein flexibility

    OpenAIRE

    Bornot, Aurélie; Offmann, Bernard; De Brevern, Alexandre

    2007-01-01

    Protein structures and protein structural models are great tools to reach protein function and provide very relevant information for drug design. Nevertheless, protein structures are not rigid entities. Cutting-edge bioinformatics methods tend to take into account the flexibility of these macromolecules. We present new approaches used to define protein structure flexibility.

  1. Total protein

    Science.gov (United States)

    The total protein test measures the total amount of two classes of proteins found in the fluid portion of your ... nutritional problems, kidney disease or liver disease . If total protein is abnormal, you will need to have more ...

  2. Interfacial Protein-Protein Associations

    OpenAIRE

    Langdon, Blake B.; Kastantin, Mark; Walder, Robert; Schwartz, Daniel K.

    2013-01-01

    While traditional models of protein adsorption focus primarily on direct protein-surface interactions, recent findings suggest that protein-protein interactions may play a central role. Using high-throughput intermolecular resonance energy transfer (RET) tracking, we directly observed dynamic, protein-protein associations of bovine serum albumin on poly(ethylene glycol) modified surfaces. The associations were heterogeneous and reversible, and associating molecules resided on the surface for ...

  3. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  4. Protein Structure

    Science.gov (United States)

    Asmus, Elaine Garbarino

    2007-01-01

    Individual students model specific amino acids and then, through dehydration synthesis, a class of students models a protein. The students clearly learn amino acid structure, primary, secondary, tertiary, and quaternary structure in proteins and the nature of the bonds maintaining a protein's shape. This activity is fun, concrete, inexpensive and…

  5. Tau protein

    DEFF Research Database (Denmark)

    Frederiksen, Jette Lautrup Battistini; Kristensen, Kim; Bahl, Jmc;

    2011-01-01

    Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. Objective: To investigate the association between tau protein concentration and 14...... the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. Results: The study shows a significantly increased...... concentration of tau protein in CSF from patients with relapsing-remitting MS and patients monosymptomatic at onset who progressed to MS, but interestingly no increased tau protein concentration in monosymptomatic ON. The concentration of tau protein was significantly correlated to Expanded Disability Status...

  6. Protein politics

    OpenAIRE

    Vijver, Marike

    2005-01-01

    This study is part of the program of the interdisciplinary research group Profetas (protein foods, environment, technology and society). Profetas consists of technological, environmental and socio-economic research projects on protein food systems which result in the development of scenarios and strategies for guiding a shift towards a more plant protein based diet. The different research projects focus on the goal of identifying viable options for a more sustainable food system. Profetas aro...

  7. Principles of protein-protein interactions.

    OpenAIRE

    Jones, S; Thornton, J. M.

    1996-01-01

    This review examines protein complexes in the Brookhaven Protein Databank to gain a better understanding of the principles governing the interactions involved in protein-protein recognition. The factors that influence the formation of protein-protein complexes are explored in four different types of protein-protein complexes--homodimeric proteins, heterodimeric proteins, enzyme-inhibitor complexes, and antibody-protein complexes. The comparison between the complexes highlights differences tha...

  8. Protein-Protein Interaction Databases

    DEFF Research Database (Denmark)

    Szklarczyk, Damian; Jensen, Lars Juhl

    2015-01-01

    of research are explored. Here we present an overview of the most widely used protein-protein interaction databases and the methods they employ to gather, combine, and predict interactions. We also point out the trade-off between comprehensiveness and accuracy and the main pitfall scientists have to be aware...

  9. Whey Protein

    Science.gov (United States)

    ... quality of life in people with mitochondrial diseases. Ovarian cysts (Polycystic ovarian syndrome). Early research suggests that taking ... weight, fat mass, and cholesterol in people with ovarian cysts. However, whey protein does not improve blood sugar ...

  10. Protein Crystallization

    Science.gov (United States)

    Chernov, Alexander A.

    2005-01-01

    Nucleation, growth and perfection of protein crystals will be overviewed along with crystal mechanical properties. The knowledge is based on experiments using optical and force crystals behave similar to inorganic crystals, though with a difference in orders of magnitude in growing parameters. For example, the low incorporation rate of large biomolecules requires up to 100 times larger supersaturation to grow protein, rather than inorganic crystals. Nucleation is often poorly reproducible, partly because of turbulence accompanying the mixing of precipitant with protein solution. Light scattering reveals fluctuations of molecular cluster size, its growth, surface energies and increased clustering as protein ages. Growth most often occurs layer-by-layer resulting in faceted crystals. New molecular layer on crystal face is terminated by a step where molecular incorporation occurs. Quantitative data on the incorporation rate will be discussed. Rounded crystals with molecularly disordered interfaces will be explained. Defects in crystals compromise the x-ray diffraction resolution crucially needed to find the 3D atomic structure of biomolecules. The defects are immobile so that birth defects stay forever. All lattice defects known for inorganics are revealed in protein crystals. Contribution of molecular conformations to lattice disorder is important, but not studied. This contribution may be enhanced by stress field from other defects. Homologous impurities (e.g., dimers, acetylated molecules) are trapped more willingly by a growing crystal than foreign protein impurities. The trapped impurities induce internal stress eliminated in crystals exceeding a critical size (part of mni for ferritin, lysozyme). Lesser impurities are trapped from stagnant, as compared to the flowing, solution. Freezing may induce much more defects unless quickly amorphysizing intracrystalline water.

  11. Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement Disorder in Progressed Stages of Late-Infantile CLN2 Disease.

    Science.gov (United States)

    Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas

    2016-06-01

    Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. PMID:27043294

  12. Using Stem Cells to Model Diseases of the Outer Retina

    Directory of Open Access Journals (Sweden)

    Camille Yvon

    2015-01-01

    Full Text Available Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE. It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP, Usher syndrome (USH, Leber congenital amaurosis (LCA, gyrate atrophy (GA, juvenile neuronal ceroid lipofuscinosis (NCL, Best vitelliform macular dystrophy (BVMD and age related macular degeneration (AMD.

  13. Arabinogalactan proteins

    DEFF Research Database (Denmark)

    Knoch, Eva; Dilokpimol, Adiphol; Geshi, Naomi

    2014-01-01

    Arabinogalactan proteins (AGPs) are a highly diverse class of cell surface proteoglycans that are commonly found in most plant species. AGPs play important roles in many cellular processes during plant development, such as reproduction, cell proliferation, pattern formation and growth, and in plant...

  14. Prediction of Protein-Protein Interactions Related to Protein Complexes Based on Protein Interaction Networks

    OpenAIRE

    Peng Liu; Lei Yang; Daming Shi; Xianglong Tang

    2015-01-01

    A method for predicting protein-protein interactions based on detected protein complexes is proposed to repair deficient interactions derived from high-throughput biological experiments. Protein complexes are pruned and decomposed into small parts based on the adaptive k-cores method to predict protein-protein interactions associated with the complexes. The proposed method is adaptive to protein complexes with different structure, number, and size of nodes in a protein-protein interaction net...

  15. Grafting of protein-protein binding sites

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A strategy for grafting protein-protein binding sites is described. Firstly, key interaction residues at the interface of ligand protein to be grafted are identified and suitable positions in scaffold protein for grafting these key residues are sought. Secondly, the scaffold proteins are superposed onto the ligand protein based on the corresponding Ca and Cb atoms. The complementarity between the scaffold protein and the receptor protein is evaluated and only matches with high score are accepted. The relative position between scaffold and receptor proteins is adjusted so that the interface has a reasonable packing density. Then the scaffold protein is mutated to corresponding residues in ligand protein at each candidate position. And the residues having bad steric contacts with the receptor proteins, or buried charged residues not involved in the formation of any salt bridge are mutated. Finally, the mutated scaffold protein in complex with receptor protein is co-minimized by Charmm. In addition, we deduce a scoring function to evaluate the affinity between mutated scaffold protein and receptor protein by statistical analysis of rigid binding data sets.

  16. Detecting overlapping protein complexes in protein-protein interaction networks

    OpenAIRE

    Nepusz, Tamás; Yu, Haiyuan; Paccanaro, Alberto

    2012-01-01

    We introduce clustering with overlapping neighborhood expansion (ClusterONE), a method for detecting potentially overlapping protein complexes from protein-protein interaction data. ClusterONE-derived complexes for several yeast data sets showed better correspondence with reference complexes in the Munich Information Center for Protein Sequence (MIPS) catalog and complexes derived from the Saccharomyces Genome Database (SGD) than the results of seven popular methods. The results also showed a...

  17. EDITORIAL: Precision proteins Precision proteins

    Science.gov (United States)

    Demming, Anna

    2010-06-01

    Since the birth of modern day medicine, during the times of Hippocrates in ancient Greece, the profession has developed from the rudimentary classification of disease into a rigorous science with an inspiring capability to treat and cure. Scientific methodology has distilled clinical diagnostic tools from the early arts of prognosis, which used to rely as much on revelation and prophecy, as intuition and judgement [1]. Over the past decade, research into the interactions between proteins and nanosystems has provided some ingenious and apt techniques for delving into the intricacies of anatomical systems. In vivo biosensing has emerged as a vibrant field of research, as much of medical diagnosis relies on the detection of substances or an imbalance in the chemicals in the body. The inherent properties of nanoscale structures, such as cantilevers, make them well suited to biosensing applications that demand the detection of molecules at very low concentrations. Measurable deflections in cantilevers functionalised with antibodies provide quantitative indicators of the presence of specific antigens when the two react. Such developments have roused mounting interest in the interactions of proteins with nanostructures, such as carbon nanotubes [3], which have demonstrated great potential as generic biomarkers. Plasmonic properties are also being exploited in sensing applications, such as the molecular sentinel recently devised by researchers in the US. The device uses the plasmonic properties of a silver nanoparticle linked to a Raman labelled hairpin DNA probe to signal changes in the probe geometry resulting from interactions with substances in the environment. Success stories so far include the detection of two specific genes associated with breast cancer [4]. A greater understanding of how RNA interference regulates gene expression has highlighted the potential of using this natural process as another agent for combating disease in personalized medicine. However, the

  18. Protein Crystal Based Nanomaterials

    Science.gov (United States)

    Bell, Jeffrey A.; VanRoey, Patrick

    2001-01-01

    This is the final report on a NASA Grant. It concerns a description of work done, which includes: (1) Protein crystals cross-linked to form fibers; (2) Engineering of protein to favor crystallization; (3) Better knowledge-based potentials for protein-protein contacts; (4) Simulation of protein crystallization.

  19. Shotgun protein sequencing.

    Energy Technology Data Exchange (ETDEWEB)

    Faulon, Jean-Loup Michel; Heffelfinger, Grant S.

    2009-06-01

    A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

  20. Protein-protein complexation in bioluminescence

    OpenAIRE

    Titushin, Maxim S.; Feng, Yingang; Lee, John; Vysotski, Eugene S.; Liu, Zhi-jie

    2011-01-01

    In this review we summarize the progress made towards understanding the role of protein-protein interactions in the function of various bioluminescence systems of marine organisms, including bacteria, jellyfish and soft corals, with particular focus on methodology used to detect and characterize these interactions. In some bioluminescence systems, protein-protein interactions involve an “accessory protein” whereby a stored substrate is efficiently delivered to the bioluminescent enzyme lucife...

  1. Protein folding, protein homeostasis, and cancer

    Institute of Scientific and Technical Information of China (English)

    John H. Van Drie

    2011-01-01

    Proteins fold into their functional 3-dimensional structures from a linear amino acid sequence. In vitro this process is spontaneous; while in vivo it is orchestrated by a specialized set of proteins, called chaperones. Protein folding is an ongoing cellular process, as cellular proteins constantly undergo synthesis and degradation. Here emerging links between this process and cancer are reviewed. This perspective both yields insights into the current struggle to develop novel cancer chemotherapeutics and has implications for future chemotherapy discovery.

  2. Protein-Protein Interaction Analysis by Docking

    OpenAIRE

    Stephan Ederer; Florian Fink; Wolfram Gronwald

    2009-01-01

    Based on a protein-protein docking approach we have developed a procedure to verify or falsify protein-protein interactions that were proposed by other methods such as yeast-2-hybrid assays. Our method currently utilizes intermolecular energies but can be expanded to incorporate additional terms such as amino acid based pair-potentials. We show some early results that demonstrate the general applicability of our approach.

  3. Protein-losing enteropathy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007338.htm Protein-losing enteropathy To use the sharing features on this page, please enable JavaScript. Protein-losing enteropathy is an abnormal loss of protein ...

  4. Protein and Heart Health

    Science.gov (United States)

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Protein and Heart Health Updated:May 5,2015 Protein ... said. What’s the harm in getting too much protein? The main problem is that often the extra ...

  5. SPIDer: Saccharomyces protein-protein interaction database

    Directory of Open Access Journals (Sweden)

    Li Zhenbo

    2006-12-01

    Full Text Available Abstract Background Since proteins perform their functions by interacting with one another and with other biomolecules, reconstructing a map of the protein-protein interactions of a cell, experimentally or computationally, is an important first step toward understanding cellular function and machinery of a proteome. Solely derived from the Gene Ontology (GO, we have defined an effective method of reconstructing a yeast protein interaction network by measuring relative specificity similarity (RSS between two GO terms. Description Based on the RSS method, here, we introduce a predicted Saccharomyces protein-protein interaction database called SPIDer. It houses a gold standard positive dataset (GSP with high confidence level that covered 79.2% of the high-quality interaction dataset. Our predicted protein-protein interaction network reconstructed from the GSPs consists of 92 257 interactions among 3600 proteins, and forms 23 connected components. It also provides general links to connect predicted protein-protein interactions with three other databases, DIP, BIND and MIPS. An Internet-based interface provides users with fast and convenient access to protein-protein interactions based on various search features (searching by protein information, GO term information or sequence similarity. In addition, the RSS value of two GO terms in the same ontology, and the inter-member interactions in a list of proteins of interest or in a protein complex could be retrieved. Furthermore, the database presents a user-friendly graphical interface which is created dynamically for visualizing an interaction sub-network. The database is accessible at http://cmb.bnu.edu.cn/SPIDer/index.html. Conclusion SPIDer is a public database server for protein-protein interactions based on the yeast genome. It provides a variety of search options and graphical visualization of an interaction network. In particular, it will be very useful for the study of inter-member interactions

  6. PIC: Protein Interactions Calculator

    OpenAIRE

    Tina, KG; Bhadra, R.; Srinivasan, N.

    2007-01-01

    Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein structure or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bo...

  7. Drugging Membrane Protein Interactions.

    Science.gov (United States)

    Yin, Hang; Flynn, Aaron D

    2016-07-11

    The majority of therapeutics target membrane proteins, accessible on the surface of cells, to alter cellular signaling. Cells use membrane proteins to transduce signals into cells, transport ions and molecules, bind cells to a surface or substrate, and catalyze reactions. Newly devised technologies allow us to drug conventionally "undruggable" regions of membrane proteins, enabling modulation of protein-protein, protein-lipid, and protein-nucleic acid interactions. In this review, we survey the state of the art of high-throughput screening and rational design in drug discovery, and we evaluate the advances in biological understanding and technological capacity that will drive pharmacotherapy forward against unorthodox membrane protein targets. PMID:26863923

  8. PREFACE: Protein protein interactions: principles and predictions

    Science.gov (United States)

    Nussinov, Ruth; Tsai, Chung-Jung

    2005-06-01

    Proteins are the `workhorses' of the cell. Their roles span functions as diverse as being molecular machines and signalling. They carry out catalytic reactions, transport, form viral capsids, traverse membranes and form regulated channels, transmit information from DNA to RNA, making possible the synthesis of new proteins, and they are responsible for the degradation of unnecessary proteins and nucleic acids. They are the vehicles of the immune response and are responsible for viral entry into the cell. Given their importance, considerable effort has been centered on the prediction of protein function. A prime way to do this is through identification of binding partners. If the function of at least one of the components with which the protein interacts is known, that should let us assign its function(s) and the pathway(s) in which it plays a role. This holds since the vast majority of their chores in the living cell involve protein-protein interactions. Hence, through the intricate network of these interactions we can map cellular pathways, their interconnectivities and their dynamic regulation. Their identification is at the heart of functional genomics; their prediction is crucial for drug discovery. Knowledge of the pathway, its topology, length, and dynamics may provide useful information for forecasting side effects. The goal of predicting protein-protein interactions is daunting. Some associations are obligatory, others are continuously forming and dissociating. In principle, from the physical standpoint, any two proteins can interact, but under what conditions and at which strength? The principles of protein-protein interactions are general: the non-covalent interactions of two proteins are largely the outcome of the hydrophobic effect, which drives the interactions. In addition, hydrogen bonds and electrostatic interactions play important roles. Thus, many of the interactions observed in vitro are the outcome of experimental overexpression. Protein disorder

  9. Protein sequence comparison and protein evolution

    Energy Technology Data Exchange (ETDEWEB)

    Pearson, W.R. [Univ. of Virginia, Charlottesville, VA (United States). Dept. of Biochemistry

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. This tutorial examines how the information conserved during the evolution of a protein molecule can be used to infer reliably homology, and thus a shared proteinfold and possibly a shared active site or function. The authors start by reviewing a geological/evolutionary time scale. Next they look at the evolution of several protein families. During the tutorial, these families will be used to demonstrate that homologous protein ancestry can be inferred with confidence. They also examine different modes of protein evolution and consider some hypotheses that have been presented to explain the very earliest events in protein evolution. The next part of the tutorial will examine the technical aspects of protein sequence comparison. Both optimal and heuristic algorithms and their associated parameters that are used to characterize protein sequence similarities are discussed. Perhaps more importantly, they survey the statistics of local similarity scores, and how these statistics can both be used to improve the selectivity of a search and to evaluate the significance of a match. They them examine distantly related members of three protein families, the serine proteases, the glutathione transferases, and the G-protein-coupled receptors (GCRs). Finally, the discuss how sequence similarity can be used to examine internal repeated or mosaic structures in proteins.

  10. Prediction of Protein-Protein Interactions Using Protein Signature Profiling

    Institute of Scientific and Technical Information of China (English)

    Mahmood; A.; Mahdavi; Yen-Han; Lin

    2007-01-01

    Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain inter- actions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as "interacting". In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis ele- gans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area un- der the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs in- creased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on aver- age 4 times better than those predicted by either phylogenetic profiling or gene expression profiling.

  11. Urine Protein and Urine Protein to Creatinine Ratio

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? Urine Protein and Urine Protein to Creatinine Ratio Share this page: Was this page helpful? Also known as: 24-Hour Urine Protein; Urine Total Protein; Urine Protein to Creatinine Ratio; ...

  12. Protein- protein interaction detection system using fluorescent protein microdomains

    Science.gov (United States)

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2010-02-23

    The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

  13. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann

    2013-01-01

    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, whereas vertebrates contain two to four genes. In cnidarians, the gene appears to encode a secreted protein, but transmembrane isoforms of the protein have also evolved, and in many species, alternative splicing facilitates the expression of both transmembrane and secreted isoforms. In most species, the...... longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...

  14. Surface Mediated Protein Disaggregation

    Science.gov (United States)

    Radhakrishna, Mithun; Kumar, Sanat K.

    2014-03-01

    Preventing protein aggregation is of both biological and industrial importance. Biologically these aggregates are known to cause amyloid type diseases like Alzheimer's and Parkinson's disease. Protein aggregation leads to reduced activity of the enzymes in industrial applications. Inter-protein interactions between the hydrophobic residues of the protein are known to be the major driving force for protein aggregation. In the current paper we show how surface chemistry and curvature can be tuned to mitigate these inter-protein interactions. Our results calculated in the framework of the Hydrophobic-Polar (HP) lattice model show that, inter-protein interactions can be drastically reduced by increasing the surface hydrophobicity to a critical value corresponding to the adsorption transition of the protein. At this value of surface hydrophobicity, proteins lose inter-protein contacts to gain surface contacts and thus the surface helps in reducing the inter-protein interactions. Further, we show that the adsorption of the proteins inside hydrophobic pores of optimal sizes are most efficient both in reducing inter-protein contacts and simultaneously retaining most of the native-contacts due to strong protein-surface interactions coupled with stabilization due to the confinement. Department of Energy (Grant No DE-FG02-11ER46811).

  15. Discover protein sequence signatures from protein-protein interaction data

    Directory of Open Access Journals (Sweden)

    Haasl Ryan J

    2005-11-01

    Full Text Available Abstract Background The development of high-throughput technologies such as yeast two-hybrid systems and mass spectrometry technologies has made it possible to generate large protein-protein interaction (PPI datasets. Mining these datasets for underlying biological knowledge has, however, remained a challenge. Results A total of 3108 sequence signatures were found, each of which was shared by a set of guest proteins interacting with one of 944 host proteins in Saccharomyces cerevisiae genome. Approximately 94% of these sequence signatures matched entries in InterPro member databases. We identified 84 distinct sequence signatures from the remaining 172 unknown signatures. The signature sharing information was then applied in predicting sub-cellular localization of yeast proteins and the novel signatures were used in identifying possible interacting sites. Conclusion We reported a method of PPI data mining that facilitated the discovery of novel sequence signatures using a large PPI dataset from S. cerevisiae genome as input. The fact that 94% of discovered signatures were known validated the ability of the approach to identify large numbers of signatures from PPI data. The significance of these discovered signatures was demonstrated by their application in predicting sub-cellular localizations and identifying potential interaction binding sites of yeast proteins.

  16. Polymer Directed Protein Assemblies

    Directory of Open Access Journals (Sweden)

    Patrick van Rijn

    2013-05-01

    Full Text Available Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

  17. Protein Dynamics in an RNA Binding Protein

    Science.gov (United States)

    Hall, Kathleen

    2006-03-01

    Using ^15N NMR relaxation measurements, analyzed with the Lipari-Szabo formalism, we have found that the human U1A RNA binding protein has ps-ns motions in those loops that make contact with RNA. Specific mutations can alter the extent and pattern of motions, and those proteins inevitably lose RNA binding affinity. Proteins with enhanced mobility of loops and termini presumably lose affinity due to increased conformational sampling by those parts of the protein that interact directly with RNA. There is an entropic penalty associated with locking down those elements upon RNA binding, in addition to a loss of binding efficiency caused by the increased number of conformations adopted by the protein. However, in addition to local conformational heterogeneity, analysis of molecular dynamics trajectories by Reorientational Eigenmode Dynamics reveals that loops of the wild type protein undergo correlated motions that link distal sites across the binding surface. Mutations that disrupt correlated motions result in weaker RNA binding, implying that there is a network of interactions across the surface of the protein. (KBH was a Postdoctoral Fellow with Al Redfield from 1985-1990). This work was supported by the NIH (to KBH) and NSF (SAS).

  18. Anisotropic Contributions to Protein-Protein Interactions.

    Science.gov (United States)

    Quang, Leigh J; Sandler, Stanley I; Lenhoff, Abraham M

    2014-02-11

    The anisotropy of shape and functionality of proteins complicates the prediction of protein-protein interactions. We examine the distribution of electrostatic and nonelectrostatic contributions to these interactions for two globular proteins, lysozyme and chymosin B, which differ in molecular weight by about a factor of 2. The interaction trends for these proteins are computed in terms of contributions to the osmotic second virial coefficient that are evaluated using atomistic models of the proteins. Our emphasis is on identifying the orientational configurations that contribute most strongly to the overall interactions due to high-complementarity interactions, and on calculating the effect of ionic strength on such interactions. The results emphasize the quantitative importance of several features of protein interactions, notably that despite differences in their frequency of occurrence, configurations differing appreciably in interaction energy can contribute meaningfully to overall interactions. However, relatively small effects due to charge anisotropy or specific hydration can affect the overall interaction significantly only if they contribute to strongly attractive configurations. The results emphasize the necessity of accounting for detailed anisotropy to capture actual experimental trends, and the sensitivity of even very detailed atomistic models to subtle solution contributions. PMID:26580057

  19. Protein Data Bank (PDB)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Protein Data Bank (PDB) archive is the single worldwide repository of information about the 3D structures of large biological molecules, including proteins and...

  20. [Protein-losing enteropathy].

    Science.gov (United States)

    Amiot, A

    2015-07-01

    Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation. PMID:25618488

  1. Protein (Cyanobacteria): 360792 [

    Lifescience Database Archive (English)

    Full Text Available YP_007146453.1 1117:17211 1161:2741 1162:3098 56106:1490 142864:1490 56107:1490 putative stress ... protein (general stress ... protein 26) Cylindrospermum stagnale PCC 7417 MTTS ...

  2. Hydrodynamic effects in proteins

    Science.gov (United States)

    Szymczak, Piotr; Cieplak, Marek

    2011-01-01

    Experimental and numerical results pertaining to flow-induced effects in proteins are reviewed. Special emphasis is placed on shear-induced unfolding and on the role of solvent mediated hydrodynamic interactions in the conformational transitions in proteins.

  3. Hydrodynamic effects in proteins

    Energy Technology Data Exchange (ETDEWEB)

    Szymczak, Piotr [Institute of Theoretical Physics, Faculty of Physics, University of Warsaw, Hoza 69, 00-681 Warsaw (Poland); Cieplak, Marek, E-mail: piotr.szymczak@fuw.edu.pl [Institute of Physics, Polish Academy of Sciences, Aleja Lotnikow 32/46, 02-668 Warsaw (Poland)

    2011-01-26

    Experimental and numerical results pertaining to flow-induced effects in proteins are reviewed. Special emphasis is placed on shear-induced unfolding and on the role of solvent mediated hydrodynamic interactions in the conformational transitions in proteins. (topical review)

  4. Protein electrophoresis - serum

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003540.htm Protein electrophoresis - serum To use the sharing features on ... JavaScript. This lab test measures the types of protein in the fluid (serum) part of a blood ...

  5. Protein: CAD [Trypanosomes Database

    Lifescience Database Archive (English)

    Full Text Available CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotaseCAD trifunct ... ional protein carbamoylphosphate synthetase 2/aspartate transcarb ... amylase/dihydroorotasemultifunctional protein ... CAD H.sapiens 47458828 18105007 790 P27708 CAD_(ge ...

  6. Learning about Proteins

    Science.gov (United States)

    ... need from peanuts alone, but if you have peanut butter on whole-grain bread, you're set. Likewise, ... protein in a day: 2 tablespoons (15 milliliters) peanut butter (7 grams protein) 1 cup (240 milliliters) low- ...

  7. Electrophoretic Separation of Proteins

    OpenAIRE

    Chakavarti, Bulbul; Chakavarti, Deb

    2008-01-01

    Electrophoresis is used to separate complex mixtures of proteins (e.g., from cells, subcellular fractions, column fractions, or immunoprecipitates), to investigate subunit compositions, and to verify homogeneity of protein samples. It can also serve to purify proteins for use in further applications. In polyacrylamide gel electrophoresis, proteins migrate in response to an electrical field through pores in a polyacrylamide gel matrix; pore size decreases with increasing acrylamide concentrati...

  8. Simulations of protein folding

    International Nuclear Information System (INIS)

    We have developed a simple, phenomenological, Monte-Carlo code that predicts the three-dimensional structure of globular proteins from the DNA sequences that define them. We have applied this code to two small proteins, the villin headpiece (1VII) and colel rop (1ROP). Our code folds both proteins to within 5 A rms of their native structures

  9. Destabilized bioluminescent proteins

    Science.gov (United States)

    Allen, Michael S.; Rakesh, Gupta; Gary, Sayler S.

    2007-07-31

    Purified nucleic acids, vectors and cells containing a gene cassette encoding at least one modified bioluminescent protein, wherein the modification includes the addition of a peptide sequence. The duration of bioluminescence emitted by the modified bioluminescent protein is shorter than the duration of bioluminescence emitted by an unmodified form of the bioluminescent protein.

  10. Protein domain prediction

    NARCIS (Netherlands)

    Ingolfsson, Helgi; Yona, Golan

    2008-01-01

    Domains are considered to be the building blocks of protein structures. A protein can contain a single domain or multiple domains, each one typically associated with a specific function. The combination of domains determines the function of the protein, its subcellular localization and the interacti

  11. CSF total protein

    Science.gov (United States)

    CSF total protein is a test to determine the amount of protein in your spinal fluid, also called cerebrospinal fluid (CSF). ... The normal protein range varies from lab to lab, but is typically about 15 to 60 mg/dL. Note: mg/dL = ...

  12. Modeling Protein Domain Function

    Science.gov (United States)

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  13. Protein - Which is Best?

    Science.gov (United States)

    Hoffman, Jay R; Falvo, Michael J

    2004-09-01

    Protein intake that exceeds the recommended daily allowance is widely accepted for both endurance and power athletes. However, considering the variety of proteins that are available much less is known concerning the benefits of consuming one protein versus another. The purpose of this paper is to identify and analyze key factors in order to make responsible recommendations to both the general and athletic populations. Evaluation of a protein is fundamental in determining its appropriateness in the human diet. Proteins that are of inferior content and digestibility are important to recognize and restrict or limit in the diet. Similarly, such knowledge will provide an ability to identify proteins that provide the greatest benefit and should be consumed. The various techniques utilized to rate protein will be discussed. Traditionally, sources of dietary protein are seen as either being of animal or vegetable origin. Animal sources provide a complete source of protein (i.e. containing all essential amino acids), whereas vegetable sources generally lack one or more of the essential amino acids. Animal sources of dietary protein, despite providing a complete protein and numerous vitamins and minerals, have some health professionals concerned about the amount of saturated fat common in these foods compared to vegetable sources. The advent of processing techniques has shifted some of this attention and ignited the sports supplement marketplace with derivative products such as whey, casein and soy. Individually, these products vary in quality and applicability to certain populations. The benefits that these particular proteins possess are discussed. In addition, the impact that elevated protein consumption has on health and safety issues (i.e. bone health, renal function) are also reviewed. Key PointsHigher protein needs are seen in athletic populations.Animal proteins is an important source of protein, however potential health concerns do exist from a diet of protein

  14. Highly thermostable fluorescent proteins

    Science.gov (United States)

    Bradbury, Andrew M.; Waldo, Geoffrey S.; Kiss, Csaba

    2011-03-22

    Thermostable fluorescent proteins (TSFPs), methods for generating these and other stability-enhanced proteins, polynucleotides encoding such proteins, and assays and method for using the TSFPs and TSFP-encoding nucleic acid molecules are provided. The TSFPs of the invention show extremely enhanced levels of stability and thermotolerance. In one case, for example, a TSFP of the invention is so stable it can be heated to 99.degree. C. for short periods of time without denaturing, and retains 85% of its fluorescence when heated to 80.degree. C. for several minutes. The invention also provides a method for generating stability-enhanced variants of a protein, including but not limited to fluorescent proteins.

  15. Protein hydration and dynamics

    International Nuclear Information System (INIS)

    Inelastic neutron scattering can measure the protein thermal fluctuations under the physiological aqueous environment, especially it is powerful to observe the low-energy protein dynamics in THz region, which are revealed theoretically to be coupled with solvations. Neutron enables the selective observation of protein and hydration water by deuteration. The complementary analysis with molecular dynamics simulation is also effective for the study of protein hydration. Some examples of the application toward the understanding of molecular basis of protein functions will be introduced. (author)

  16. Protein crystallization with paper

    Science.gov (United States)

    Matsuoka, Miki; Kakinouchi, Keisuke; Adachi, Hiroaki; Maruyama, Mihoko; Sugiyama, Shigeru; Sano, Satoshi; Yoshikawa, Hiroshi Y.; Takahashi, Yoshinori; Yoshimura, Masashi; Matsumura, Hiroyoshi; Murakami, Satoshi; Inoue, Tsuyoshi; Mori, Yusuke; Takano, Kazufumi

    2016-05-01

    We developed a new protein crystallization method that incorporates paper. A small piece of paper, such as facial tissue or KimWipes, was added to a drop of protein solution in the traditional sitting drop vapor diffusion technique, and protein crystals grew by incorporating paper. By this method, we achieved the growth of protein crystals with reducing osmotic shock. Because the technique is very simple and the materials are easy to obtain, this method will come into wide use for protein crystallization. In the future, it could be applied to nanoliter-scale crystallization screening on a paper sheet such as in inkjet printing.

  17. Protein and vegetarian diets.

    Science.gov (United States)

    Marsh, Kate A; Munn, Elizabeth A; Baines, Surinder K

    2013-08-19

    A vegetarian diet can easily meet human dietary protein requirements as long as energy needs are met and a variety of foods are eaten. Vegetarians should obtain protein from a variety of plant sources, including legumes, soy products, grains, nuts and seeds. Eggs and dairy products also provide protein for those following a lacto-ovo-vegetarian diet. There is no need to consciously combine different plant proteins at each meal as long as a variety of foods are eaten from day to day, because the human body maintains a pool of amino acids which can be used to complement dietary protein. The consumption of plant proteins rather than animal proteins by vegetarians may contribute to their reduced risk of chronic diseases such as diabetes and heart disease. PMID:25369930

  18. Protein kinesis: The dynamics of protein trafficking and stability

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    The purpose of this conference is to provide a multidisciplinary forum for exchange of state-of-the-art information on protein kinesis. This volume contains abstracts of papers in the following areas: protein folding and modification in the endoplasmic reticulum; protein trafficking; protein translocation and folding; protein degradation; polarity; nuclear trafficking; membrane dynamics; and protein import into organelles.

  19. Protein Electrophoresis/Immunofixation Electrophoresis

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Protein Electrophoresis Immunofixation Electrophoresis Share this page: Was this page helpful? Also known as: Serum Protein Electrophoresis; Protein ELP; SPE; SPEP; Urine Protein Electrophoresis; ...

  20. Protein: FEB6 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FEB6 Photoresponse regulatory proteins HD1 SE1 Zinc finger protein HD1 Protein CONSTANS-like, Pr ... otein HEADING DATE 1, Protein PHOTOPERIOD SENSITIVITY ... 1 39947 Oryza sativa subsp. japonica 4340746 Q9FDX ...

  1. Identifying novel protein phenotype annotations by hybridizing protein-protein interactions and protein sequence similarities.

    Science.gov (United States)

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-04-01

    Studies of protein phenotypes represent a central challenge of modern genetics in the post-genome era because effective and accurate investigation of protein phenotypes is one of the most critical procedures to identify functional biological processes in microscale, which involves the analysis of multifactorial traits and has greatly contributed to the development of modern biology in the post genome era. Therefore, we have developed a novel computational method that identifies novel proteins associated with certain phenotypes in yeast based on the protein-protein interaction network. Unlike some existing network-based computational methods that identify the phenotype of a query protein based on its direct neighbors in the local network, the proposed method identifies novel candidate proteins for a certain phenotype by considering all annotated proteins with this phenotype on the global network using a shortest path (SP) algorithm. The identified proteins are further filtered using both a permutation test and their interactions and sequence similarities to annotated proteins. We compared our method with another widely used method called random walk with restart (RWR). The biological functions of proteins for each phenotype identified by our SP method and the RWR method were analyzed and compared. The results confirmed a large proportion of our novel protein phenotype annotation, and the RWR method showed a higher false positive rate than the SP method. Our method is equally effective for the prediction of proteins involving in all the eleven clustered yeast phenotypes with a quite low false positive rate. Considering the universality and generalizability of our supporting materials and computing strategies, our method can further be applied to study other organisms and the new functions we predicted can provide pertinent instructions for the further experimental verifications. PMID:26728152

  2. Sensitizing properties of proteins

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Ladics, Gregory S; McClain, Scott;

    2014-01-01

    The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding the...... relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein...... scientists from academia, government, and industry participated in the symposium. Experts provided overviews on known mechanisms by which proteins in food may cause sensitization, discussed experimental models to predict protein sensitizing potential, and explored whether such experimental techniques may be...

  3. NMR of unfolded proteins

    Indian Academy of Sciences (India)

    Amarnath Chtterjee; Ashutosh Kumar; Jeetender Chugh; Sudha Srivastava; Neel S Bhavesh; Ramakrishna V Hosur

    2005-01-01

    In the post-genomic era, as more and more genome sequences are becoming known and hectic efforts are underway to decode the information content in them, it is becoming increasingly evident that flexibility in proteins plays a crucial role in many of the biological functions. Many proteins have intrinsic disorder either wholly or in specific regions. It appears that this disorder may be important for regulatory functions of the proteins, on the one hand, and may help in directing the folding process to reach the compact native state, on the other. Nuclear magnetic resonance (NMR) has over the last two decades emerged as the sole, most powerful technique to help characterize these disordered protein systems. In this review, we first discuss the significance of disorder in proteins and then describe the recent developments in NMR methods for their characterization. A brief description of the results obtained on several disordered proteins is presented at the end.

  4. Computational Protein Design

    DEFF Research Database (Denmark)

    Johansson, Kristoffer Enøe

    to a central method that enables new developments. For example, novel enzymes with functions not found in natural proteins have been de novo designed to give enough activity for experimental optimization. This thesis presents the current state-of-the-art within computational design methods together......Proteins are the major functional group of molecules in biology. The impact of protein science on medicine and chemical productions is rapidly increasing. However, the greatest potential remains to be realized. The fi eld of protein design has advanced computational modeling from a tool of support...... with a novel method based on probability theory. With the aim of assembling a complete pipeline for protein design, this work touches upon several aspects of protein design. The presented work is the computational half of a design project where the other half is dedicated to the experimental part of...

  5. Protein Models Comparator

    CERN Document Server

    Widera, Paweł

    2011-01-01

    The process of comparison of computer generated protein structural models is an important element of protein structure prediction. It has many uses including model quality evaluation, selection of the final models from a large set of candidates or optimisation of parameters of energy functions used in template free modelling and refinement. Although many protein comparison methods are available online on numerous web servers, their ability to handle a large scale model comparison is often very limited. Most of the servers offer only a single pairwise structural comparison, and they usually do not provide a model-specific comparison with a fixed alignment between the models. To bridge the gap between the protein and model structure comparison we have developed the Protein Models Comparator (pm-cmp). To be able to deliver the scalability on demand and handle large comparison experiments the pm-cmp was implemented "in the cloud". Protein Models Comparator is a scalable web application for a fast distributed comp...

  6. Protein oxidation and peroxidation.

    Science.gov (United States)

    Davies, Michael J

    2016-04-01

    Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established. PMID:27026395

  7. Proteins at interfaces

    OpenAIRE

    Evers, Florian

    2011-01-01

    Protein adsorption is a fundamental and ubiquitous phenomenon, which has severe implications in the fields of biomaterials as well as bio- and nanotechnology, e.g., in drug delivery, biofouling, the biocompatibility of implants, food chemistry, and biosensors. Therefore, the mechanisms of protein adsorption and controlling the interfacial affinity of proteins have become intriguing and interdisciplinary research topics. In this work, X-ray and neutron reflectometry are the main...

  8. Protein-surfactant interactions

    OpenAIRE

    Valstar, Ank

    2000-01-01

    Protein-surfactant interactions in aqueous media have been investigated. The globular proteins lysozyme and bovine serum albumin (BSA) served as model proteins. Several ionic and non-ionic surfactants were used. Fluorescence probe measurements showed that at low sodium dodecyl sulfate (SDS) concentration (< 0.1 M) one micelle-like SDS cluster is bound to lysozyme. From dynamic light scattering (DLS) results it was observed that lysozyme in the complex does not correspond to the fully unfol...

  9. Pressure cryocooling protein crystals

    Science.gov (United States)

    Kim, Chae Un; Gruner, Sol M.

    2011-10-04

    Preparation of cryocooled protein crystal is provided by use of helium pressurizing and cryocooling to obtain cryocooled protein crystal allowing collection of high resolution data and by heavier noble gas (krypton or xenon) binding followed by helium pressurizing and cryocooling to obtain cryocooled protein crystal for collection of high resolution data and SAD phasing simultaneously. The helium pressurizing is carried out on crystal coated to prevent dehydration or on crystal grown in aqueous solution in a capillary.

  10. Biofilm Matrix Proteins

    OpenAIRE

    Fong, Jiunn N. C.; Yildiz, Fitnat H.

    2015-01-01

    Proteinaceous components of the biofilm matrix include secreted extracellular proteins, cell surface adhesins and protein subunits of cell appendages such as flagella and pili. Biofilm matrix proteins play diverse roles in biofilm formation and dissolution. They are involved in attaching cells to surfaces, stabilizing the biofilm matrix via interactions with exopolysaccharide and nucleic acid components, developing three-dimensional biofilm architectures, and dissolving biofilm matrix via enz...

  11. Ribosome-inactivating proteins

    OpenAIRE

    Walsh, Matthew J; Dodd, Jennifer E; Hautbergue, Guillaume M.

    2013-01-01

    Ribosome-inactivating proteins (RIPs) were first isolated over a century ago and have been shown to be catalytic toxins that irreversibly inactivate protein synthesis. Elucidation of atomic structures and molecular mechanism has revealed these proteins to be a diverse group subdivided into two classes. RIPs have been shown to exhibit RNA N-glycosidase activity and depurinate the 28S rRNA of the eukaryotic 60S ribosomal subunit. In this review, we compare archetypal RIP family members with oth...

  12. Trisulfides in Proteins

    DEFF Research Database (Denmark)

    Nielsen, Rasmus W.; Tachibana, Christine; Hansen, Niels Erik;

    2011-01-01

    post-translational modification, and the number of proteins in which a trisulfide has been unambiguously identified is small. Nevertheless, we believe that its prevalence may be underestimated, particularly with the increasing evidence for significant pools of sulfides in living tissues and their...... possible roles in cellular metabolism. This review focuses on examples of proteins that are known to contain a trisulfide bridge, and gives an overview of the chemistry of trisulfide formation, and the methods by which it is detected in proteins....

  13. Staining Proteins in Gels

    OpenAIRE

    Gallagher, Sean; Chakavarti, Deb

    2008-01-01

    Following separation by electrophoretic methods, proteins in a gel can be detected by several staining methods. This unit describes protocols for detecting proteins by four popular methods. Coomassie blue staining is an easy and rapid method. Silver staining, while more time consuming, is considerably more sensitive and can thus be used to detect smaller amounts of protein. Fluorescent staining is a popular alternative to traditional staining procedures, mainly because it is more sensitive th...

  14. Acanthamoeba castellanii STAT protein.

    Science.gov (United States)

    Kicinska, Anna; Leluk, Jacek; Jarmuszkiewicz, Wieslawa

    2014-01-01

    STAT (signal transducers and activators of transcription) proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil), a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds) or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups. PMID:25338074

  15. Acanthamoeba castellanii STAT protein.

    Directory of Open Access Journals (Sweden)

    Anna Kicinska

    Full Text Available STAT (signal transducers and activators of transcription proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil, a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

  16. Consensus protein design

    Science.gov (United States)

    Porebski, Benjamin T.; Buckle, Ashley M.

    2016-01-01

    A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering. PMID:27274091

  17. Engineering therapeutic protein disaggregases

    Science.gov (United States)

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  18. Simulations of Protein Folding

    CERN Document Server

    Cahill, M; Cahill, K E; Cahill, Michael; Fleharty, Mark; Cahill, Kevin

    2000-01-01

    We have developed a simple, phenomenological, Monte-Carlo code that predicts the three-dimensional structure of globular proteins from the DNA sequences that define them. We have applied this code to two small proteins, the villin headpiece (1VII) and cole1 rop (1ROP). Our code folded the 36-residue villin headpiece to a mean rms distance of less than 5 A from its native structure as revealed by NMR; it folded a 56-residue fragment of the protein cole1 rop to within 11 A of its native structure. The denatured starting configurations of these two proteins were, respectively, 29 A and 55 A distant from their native structures.

  19. Ultrafiltration of pegylated proteins

    Science.gov (United States)

    Molek, Jessica R.

    There is considerable clinical interest in the use of "second-generation" therapeutics produced by conjugation of a native protein with various polymers including polyethylene glycol (PEG). PEG--protein conjugates, so-called PEGylated proteins, can exhibit enhanced stability, half-life, and bioavailability. One of the challenges in the commercial production of PEGylated proteins is the purification required to remove unreacted polymer, native protein, and in many cases PEGylated proteins with nonoptimal degrees of conjugation. The overall objective of this thesis was to examine the use of ultrafiltration for the purification of PEGylated proteins. This included: (1) analysis of size-based separation of PEGylated proteins using conventional ultrafiltration membranes, (2) use of electrically-charged membranes to exploit differences in electrostatic interactions, and (3) examination of the effects of PEGylation on protein fouling. The experimental results were analyzed using appropriate theoretical models, with the underlying physical properties of the PEGylated proteins evaluated using size exclusion chromatography, capillary electrophoresis, dynamic light scattering, and reverse phase chromatography. PEGylated proteins were produced by covalent attachment of activated PEG to a protein via primary amines on the lysine residues. A simple model was developed for the reaction kinetics, which was used to explore the effect of reaction conditions and mode of operation on the distribution of PEGylated products. The effective size of the PEGylated proteins was evaluated using size exclusion chromatography, with appropriate correlations developed for the size in terms of the molecular weight of the native protein and attached PEG. The electrophoretic mobility of the PEGylated proteins were evaluated by capillary electrophoresis with the data in good agreement with a simple model accounting for the increase in protein size and the reduction in the number of protonated amine

  20. Hermansky-Pudlak syndrome: A case report

    Directory of Open Access Journals (Sweden)

    R Vani

    2014-01-01

    Full Text Available Hermansky-Pudlak syndrome (HPS is a rare autosomal recessive disorder, which results in oculocutaneous albinism, bleeding disorders, and storage of abnormal fat protein compound (liposomal accumulation of ceroid lipofuscin. The major complications of this disorder are pulmonary fibrosis (PF and colitis. This is a case report of an HPS patient with PF.

  1. How Many Protein-Protein Interactions Types Exist in Nature?

    OpenAIRE

    Garma, Leonardo; Mukherjee, Srayanta; Mitra, Pralay; Zhang, Yang

    2012-01-01

    Protein quaternary structure universe” refers to the ensemble of all protein-protein complexes across all organisms in nature. The number of quaternary folds thus corresponds to the number of ways proteins physically interact with other proteins. This study focuses on answering two basic questions: Whether the number of protein-protein interactions is limited and, if yes, how many different quaternary folds exist in nature. By all-to-all sequence and structure comparisons, we grouped the pro...

  2. How Many Protein-Protein Interactions Types Exist in Nature?

    OpenAIRE

    Leonardo Garma; Srayanta Mukherjee; Pralay Mitra; Yang Zhang

    2012-01-01

    "Protein quaternary structure universe" refers to the ensemble of all protein-protein complexes across all organisms in nature. The number of quaternary folds thus corresponds to the number of ways proteins physically interact with other proteins. This study focuses on answering two basic questions: Whether the number of protein-protein interactions is limited and, if yes, how many different quaternary folds exist in nature. By all-to-all sequence and structure comparisons, we grouped the pro...

  3. Protein (Cyanobacteria): 286011 [

    Lifescience Database Archive (English)

    Full Text Available YP_007057271.1 1117:4890 1161:684 1185:224 373984:129 373994:129 histidine kinase,PAS ... domain-con ... taining protein,PAS ... domain-containing protein,histidine kinase,GAF dom ...

  4. Protein (Viridiplantae): 357488463 [

    Lifescience Database Archive (English)

    Full Text Available XP_003614519.1 33090:2423 35493:1202 131221:1202 3193:1202 58023:2056 78536:1595 58024:1595 3398 ... 938 3814:1938 163742:3028 3877:3028 3880:3028 Cyst nematode ... resistance protein-like protein Medicago truncatul ...

  5. Poxviral Ankyrin Proteins

    Directory of Open Access Journals (Sweden)

    Michael H. Herbert

    2015-02-01

    Full Text Available Multiple repeats of the ankyrin motif (ANK are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.

  6. Protein (Viridiplantae): 186478918 [

    Lifescience Database Archive (English)

    Full Text Available NP_001117362.1 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  7. Protein (Viridiplantae): 145336153 [

    Lifescience Database Archive (English)

    Full Text Available NP_174031.2 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 71 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  8. Protein (Viridiplantae): 186478920 [

    Lifescience Database Archive (English)

    Full Text Available NP_001117363.1 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  9. Protein (Viridiplantae): 18396209 [

    Lifescience Database Archive (English)

    Full Text Available NP_564271.1 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 71 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  10. Proteins in biomass streams

    NARCIS (Netherlands)

    Mulder, W.J.

    2010-01-01

    The focus of this study is to give an overview of traditional and new biomasses and biomass streams that contain proteins. When information was available, the differences in molecular structure and physical and chemical properties for the different proteins is given. For optimal biomass use, isolati

  11. Protein (Cyanobacteria): 187726 [

    Lifescience Database Archive (English)

    Full Text Available ZP_00515693.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MHKIPVT ...

  12. Protein (Cyanobacteria): 187721 [

    Lifescience Database Archive (English)

    Full Text Available ZP_00515086.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MSGINQQ ...

  13. Protein (Cyanobacteria): 187724 [

    Lifescience Database Archive (English)

    Full Text Available ZP_00514782.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MQIVDKK ...

  14. Protein (Cyanobacteria): 187722 [

    Lifescience Database Archive (English)

    Full Text Available ZP_00515750.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MTPLNFN ...

  15. Protein (Cyanobacteria): 187723 [

    Lifescience Database Archive (English)

    Full Text Available ZP_00515087.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MTRLDFN ...

  16. Protein (Viridiplantae): 15240110 [

    Lifescience Database Archive (English)

    Full Text Available NP_201488.1 33090:325 35493:1944 131221:1944 3193:1944 58023:3713 78536:2650 58024:2650 3398:265 ... :1852 LOB domain-containing protein 36 (ASYMMETRIC LEAVES ... 2-like protein 1) Arabidopsis thaliana MASSSSPCAAC ...

  17. Protein (Viridiplantae): 357505877 [

    Lifescience Database Archive (English)

    Full Text Available XP_003623227.1 33090:2309 35493:2314 131221:2314 3193:2314 58023:1780 78536:1486 58024:1486 3398 ... 163742:9849 3877:9849 3880:9849 Cell cycle control crn ... (Crooked neck) protein-like protein Medicago trunc ...

  18. Protein (Viridiplantae): 357472389 [

    Lifescience Database Archive (English)

    Full Text Available XP_003606479.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAETSSSNN ...

  19. Protein (Viridiplantae): 357472385 [

    Lifescience Database Archive (English)

    Full Text Available XP_003606477.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAETSSSNN ...

  20. Protein (Viridiplantae): 357440307 [

    Lifescience Database Archive (English)

    Full Text Available XP_003590431.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAGTSSKIP ...

  1. Protein (Viridiplantae): 357444551 [

    Lifescience Database Archive (English)

    Full Text Available XP_003592553.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAGTSSKIP ...

  2. C-reactive protein

    Science.gov (United States)

    C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation throughout the body. It is one of a group of proteins called "acute phase reactants" that go up in response to inflammation. ...

  3. Protein (Viridiplantae): 18414878 [

    Lifescience Database Archive (English)

    Full Text Available NP_567527.1 33090:1722 35493:20777 131221:20777 3193:20777 58023:13588 78536:13546 58024:13546 3 ... 83:5979 3701:5979 3702:6150 Tryptophan RNA-binding attenuator ... protein-like protein Arabidopsis thaliana MAAPFFST ...

  4. Protein (Viridiplantae): 238480800 [

    Lifescience Database Archive (English)

    Full Text Available NP_001154247.1 33090:1722 35493:20777 131221:20777 3193:20777 58023:13588 78536:13546 58024:1354 ... 83:5979 3701:5979 3702:6150 Tryptophan RNA-binding attenuator ... protein-like protein Arabidopsis thaliana MAAPFFST ...

  5. Protein (Viridiplantae): 238480798 [

    Lifescience Database Archive (English)

    Full Text Available NP_001154246.1 33090:1722 35493:20777 131221:20777 3193:20777 58023:13588 78536:13546 58024:1354 ... 83:5979 3701:5979 3702:6150 Tryptophan RNA-binding attenuator ... protein-like protein Arabidopsis thaliana MAAPFFST ...

  6. Protein (Cyanobacteria): 305313 [

    Lifescience Database Archive (English)

    Full Text Available ZP_09781770.1 1117:5986 1150:1684 35823:2516 376219:684 Cytochrome b6-f complex iron -sulfur subu ... nit 1 (Rieske iron -sulfur protein 1) (Plastohydroquinone:plastocyanin ... oxidoreductase iron -sulfur protein 1) (ISP 1) (RISP 1) Arthrospira sp. ...

  7. Protein Attachment on Nanodiamonds.

    Science.gov (United States)

    Lin, Chung-Lun; Lin, Cheng-Huang; Chang, Huan-Cheng; Su, Meng-Chih

    2015-07-16

    A recent advance in nanotechnology is the scale-up production of small and nonaggregated diamond nanoparticles suitable for biological applications. Using detonation nanodiamonds (NDs) with an average diameter of ∼4 nm as the adsorbents, we have studied the static attachment of three proteins (myoglobin, bovine serum albumin, and insulin) onto the nanoparticles by optical spectroscopy, mass spectrometry, and dynamic light scattering, and electrophoretic zeta potential measurements. Results show that the protein surface coverage is predominantly determined by the competition between protein-protein and protein-ND interactions, giving each protein a unique and characteristic structural configuration in its own complex. Specifically, both myoglobin and bovine serum albumin show a Langmuir-type adsorption behavior, forming 1:1 complexes at saturation, whereas insulin folds into a tightly bound multimer before adsorption. The markedly different adsorption patterns appear to be independent of the protein concentration and are closely related to the affinity of the individual proteins for the NDs. The present study provides a fundamental understanding for the use of NDs as a platform for nanomedical drug delivery. PMID:25815400

  8. Protein sequence databases.

    Science.gov (United States)

    Apweiler, Rolf; Bairoch, Amos; Wu, Cathy H

    2004-02-01

    A variety of protein sequence databases exist, ranging from simple sequence repositories, which store data with little or no manual intervention in the creation of the records, to expertly curated universal databases that cover all species and in which the original sequence data are enhanced by the manual addition of further information in each sequence record. As the focus of researchers moves from the genome to the proteins encoded by it, these databases will play an even more important role as central comprehensive resources of protein information. Several the leading protein sequence databases are discussed here, with special emphasis on the databases now provided by the Universal Protein Knowledgebase (UniProt) consortium. PMID:15036160

  9. Manipulating and Visualizing Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Horst D.

    2003-12-05

    ProteinShop Gives Researchers a Hands-On Tool for Manipulating, Visualizing Protein Structures. The Human Genome Project and other biological research efforts are creating an avalanche of new data about the chemical makeup and genetic codes of living organisms. But in order to make sense of this raw data, researchers need software tools which let them explore and model data in a more intuitive fashion. With this in mind, researchers at Lawrence Berkeley National Laboratory and the University of California, Davis, have developed ProteinShop, a visualization and modeling program which allows researchers to manipulate protein structures with pinpoint control, guided in large part by their own biological and experimental instincts. Biologists have spent the last half century trying to unravel the ''protein folding problem,'' which refers to the way chains of amino acids physically fold themselves into three-dimensional proteins. This final shape, which resembles a crumpled ribbon or piece of origami, is what determines how the protein functions and translates genetic information. Understanding and modeling this geometrically complex formation is no easy matter. ProteinShop takes a given sequence of amino acids and uses visualization guides to help generate predictions about the secondary structures, identifying alpha helices and flat beta strands, and the coil regions that bind them. Once secondary structures are in place, researchers can twist and turn these pre-configurations until they come up with a number of possible tertiary structure conformations. In turn, these are fed into a computationally intensive optimization procedure that tries to find the final, three-dimensional protein structure. Most importantly, ProteinShop allows users to add human knowledge and intuition to the protein structure prediction process, thus bypassing bad configurations that would otherwise be fruitless for optimization. This saves compute cycles and accelerates

  10. MicroProteins

    DEFF Research Database (Denmark)

    Eguen, Teinai Ebimienere; Straub, Daniel; Graeff, Moritz;

    2015-01-01

    MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining...... characteristics of a miP. In this opinion article, we clearly state the characteristics of a miP as evidenced by known proteins that fit the definition; we explain why modulatory proteins misrepresented as miPs do not qualify as true miPs. We also discuss the evolutionary history of miPs, and how the miP concept...... can extend beyond transcription factors (TFs) to encompass different non-TF proteins that require dimerization for full function....

  11. The centrality of cancer proteins in human protein-protein interaction network: a revisit.

    Science.gov (United States)

    Xiong, Wei; Xie, Luyu; Zhou, Shuigeng; Liu, Hui; Guan, Jihong

    2014-01-01

    Topological analysis of protein-protein interaction (PPI) networks has been widely applied to the investigation on cancer mechanisms. However, there is still a debate on whether cancer proteins exhibit more topological centrality compared to the other proteins in the human PPI network. To resolve this debate, we first identified four sets of human proteins, and then mapped these proteins into the yeast PPI network by homologous genes. Finally, we compared these proteins' properties in human and yeast PPI networks. Experiments over two real datasets demonstrated that cancer proteins tend to have higher degree and smaller clustering coefficient than non-cancer proteins. Experimental results also validated that cancer proteins have larger betweenness centrality compared to the other proteins on the STRING dataset. However, on the BioGRID dataset, the average betweenness centrality of cancer proteins is larger than that of disease and control proteins, but smaller than that of essential proteins. PMID:24878726

  12. Protein oxidation in aquatic foods

    DEFF Research Database (Denmark)

    Baron, Caroline P.

    2014-01-01

    The chapter discusses general considerations about protein oxidation and reviews the mechanisms involved in protein oxidation and consequences of protein oxidation on fish proteins. It presents two case studies, the first deals with protein and lipid oxidation in frozen rainbow trout......, and the second with oxidation in salted herring. The mechanisms responsible for initiation of protein oxidation are unclear, but it is generally accepted that free radical species initiating lipid oxidation can also initiate protein oxidation. The chapter focuses on interaction between protein and lipid...... oxidation. The protein carbonyl group measurement is the widely used method for estimating protein oxidation in foods and has been used in fish muscle. The chapter also talks about the impact of protein oxidation on protein functionality, fish muscle texture, and food nutritional value. Protein oxidation...

  13. An Algorithm for Finding Functional Modules and Protein Complexes in Protein-Protein Interaction Networks

    OpenAIRE

    Guangyu Cui; Yu Chen; De-Shuang Huang; Kyungsook Han

    2008-01-01

    Biological processes are often performed by a group of proteins rather than by individual proteins, and proteins in a same biological group form a densely connected subgraph in a protein-protein interaction network. Therefore, finding a densely connected subgraph provides useful information to predict the function or protein complex of uncharacterized proteins in the highly connected subgraph. We have developed an efficient algorithm and program for finding cliques and near-cliques in a prote...

  14. Quantification of the Influence of Protein-Protein Interactions on Adsorbed Protein Structure and Bioactivity

    OpenAIRE

    Wei, Yang; Thyparambil, Aby A.; Latour, Robert A.

    2013-01-01

    While protein-surface interactions have been widely studied, relatively little is understood at this time regarding how protein-surface interaction effects are influenced by protein-protein interactions and how these effects combine with the internal stability of a protein to influence its adsorbed-state structure and bioactivity. The objectives of this study were to develop a method to study these combined effects under widely varying protein-protein interaction conditions using hen egg-whit...

  15. New approach for predicting protein-protein interactions

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Protein-protein interactions (PPIs) are of vital importance for virtually all processes of a living cell. The study of these associations of protein molecules could improve people's understanding of diseases and provide basis for therapeutic approaches.

  16. Analysis of correlations between protein complex and protein-protein interaction and mRNA expression

    Institute of Scientific and Technical Information of China (English)

    CAI Lun; XUE Hong; LU Hongchao; ZHAO Yi; ZHU Xiaopeng; BU Dongbo; LING Lunjiang; CHEN Runsheng

    2003-01-01

    Protein-protein interaction is a physical interaction of two proteins in living cells. In budding yeast Saccharomyces cerevisiae, large-scale protein-protein interaction data have been obtained through high-throughput yeast two-hybrid systems (Y2H) and protein complex purification techniques based on mass-spectrometry. Here, we collect 11855 interactions between total 2617 proteins. Through seriate genome-wide mRNA expression data, similarity between two genes could be measured. Protein complex data can also be obtained publicly and can be translated to pair relationship that any two proteins can only exist in the same complex or not. Analysis of protein complex data, protein-protein interaction data and mRNA expression data can elucidate correlations between them. The results show that proteins that have interactions or similar expression patterns have a higher possibility to be in the same protein complex than randomized selected proteins, and proteins which have interactions and similar expression patterns are even more possible to exist in the same protein complex. The work indicates that comprehensive integration and analysis of public large-scale bioinformatical data, such as protein complex data, protein-protein interaction data and mRNA expression data, may help to uncover their relationships and common biological information underlying these data. The strategies described here may help to integrate and analyze other functional genomic and proteomic data, such as gene expression profiling, protein-localization mapping and large-scale phenotypic data, both in yeast and in other organisms.

  17. Piezoelectric allostery of protein.

    Science.gov (United States)

    Ohnuki, Jun; Sato, Takato; Takano, Mitsunori

    2016-07-01

    Allostery is indispensable for a protein to work, where a locally applied stimulus is transmitted to a distant part of the molecule. While the allostery due to chemical stimuli such as ligand binding has long been studied, the growing interest in mechanobiology prompts the study of the mechanically stimulated allostery, the physical mechanism of which has not been established. By molecular dynamics simulation of a motor protein myosin, we found that a locally applied mechanical stimulus induces electrostatic potential change at distant regions, just like the piezoelectricity. This novel allosteric mechanism, "piezoelectric allostery", should be of particularly high value for mechanosensor/transducer proteins. PMID:27575163

  18. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  19. Protein crystallography prescreen kit

    Science.gov (United States)

    Segelke, Brent W.; Krupka, Heike I.; Rupp, Bernhard

    2005-07-12

    A kit for prescreening protein concentration for crystallization includes a multiplicity of vials, a multiplicity of pre-selected reagents, and a multiplicity of sample plates. The reagents and a corresponding multiplicity of samples of the protein in solutions of varying concentrations are placed on sample plates. The sample plates containing the reagents and samples are incubated. After incubation the sample plates are examined to determine which of the sample concentrations are too low and which the sample concentrations are too high. The sample concentrations that are optimal for protein crystallization are selected and used.

  20. Human Protein Z.

    OpenAIRE

    Broze, G J; Miletich, J P

    1984-01-01

    Protein Z was purified from human plasma by a four-step procedure which included barium citrate adsorption, ammonium sulfate fractionation, DEAE-Sepharose chromatography, and blue agarose chromatography with a yield of 20%. It is a 62,000 mol wt protein with an extinction coefficient of 12.0. The concentration of Protein Z in pooled, citrated plasma is 2.2 micrograms/ml and its half-life in patients starting warfarin anticoagulation therapy is estimated to be less than 2.5 d. The NH2-terminal...

  1. Evolution of proteins.

    Science.gov (United States)

    Dayhoff, M. O.

    1971-01-01

    The amino acid sequences of proteins from living organisms are dealt with. The structure of proteins is first discussed; the variation in this structure from one biological group to another is illustrated by the first halves of the sequences of cytochrome c, and a phylogenetic tree is derived from the cytochrome c data. The relative geological times associated with the events of this tree are discussed. Errors which occur in the duplication of cells during the evolutionary process are examined. Particular attention is given to evolution of mutant proteins, globins, ferredoxin, and transfer ribonucleic acids (tRNA's). Finally, a general outline of biological evolution is presented.

  2. The characterisation and prediction of protein-protein interfaces.

    OpenAIRE

    Kabir, T.

    2004-01-01

    Understanding how proteins interact with each other is of fundamental importance and is one of the most important goals of molecular biology. In order to study the characteristics of protein-protein interaction sites datasets of non-homologous protein-complexes have been compiled. These datasets include 142 obligate homocomplexes, 20 obligate hetero-complexes, 20 enzyme-inhibitor complexes, 15 antibody-antigen complexes, and 10 signaling complexes. Overall, the protein-protein interfaces of o...

  3. Whey Protein- The Role of Protein Supplementation in Resistance Training

    OpenAIRE

    Zimmer, Raymond

    2005-01-01

    Adequate protein intake is an important concern for many athletes who are undergoing strength-training programs. Many athletes choose to take a protein supplement, such as whey protein, in order to help them build lean muscle mass more efficiently. But the benefit of very high levels of dietary protein in resistance training remains questionable. This paper examines the effectiveness of whey protein, and other forms of protein supplements, in helping athletes augment their muscle mass. A comp...

  4. Protein-protein interaction databases: keeping up with growing interactomes

    OpenAIRE

    Lehne Benjamin; Schlitt Thomas

    2009-01-01

    Abstract Over the past few years, the number of known protein-protein interactions has increased substantially. To make this information more readily available, a number of publicly available databases have set out to collect and store protein-protein interaction data. Protein-protein interactions have been retrieved from six major databases, integrated and the results compared. The six databases (the Biological General Repository for Interaction Datasets [BioGRID], the Molecular INTeraction ...

  5. The effect of protein-protein and protein-membrane interactions on membrane fouling in ultrafiltration

    NARCIS (Netherlands)

    Huisman, I.H.; Prádanos, P.; Hernández, A.

    2000-01-01

    It was studied how protein-protein and protein-membrane interactions influence the filtration performance during the ultrafiltration of protein solutions over polymeric membranes. This was done by measuring flux, streaming potential, and protein transmission during filtration of bovine serum albumin

  6. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  7. Protein (Cyanobacteria): 292092 [

    Lifescience Database Archive (English)

    Full Text Available ZP_11392515.1 1117:5087 1150:2441 44887:135 864702:135 PAS ... domain type 3-containing protein,PAS ... STISDITSQKRTEAALQRSTARYENLASNIPGMIYQVVLETNGHFRFAYASPAS REIFGLEPEQLMKSAALGMTVIHPDDVVSFRQSIAQSAKTLQTQLGKLPK ...

  8. Protein turnover in sheep

    International Nuclear Information System (INIS)

    Considerable advances have been made in the knowledge of the mechanisms and control of synthesis and degradation of proteins in animal tissues during the last decade. Most of the work on the measurement of synthetic and degradative rates of the mixed protein fraction from tissues has been conducted in the rat. There have, unfortunately, been few publications describing results of protein turnover studies with ruminants. Consideration is given here to the techniques used to measure protein turnover, and some of the results obtained, particularly with sheep, are summarized. No attempt has been made to discuss directly the situation in parasitized animals; rather the aim is to provide background information which complements other work dealing with the effects of parasites on the nitrogen metabolism of ruminants. (author)

  9. Engineered Proteins for Bioelectrochemistry

    Science.gov (United States)

    Akram, Muhammad Safwan; Rehman, Jawad Ur; Hall, Elizabeth A. H.

    2014-06-01

    It is only in the past two decades that excellent protein engineering tools have begun to meet parallel advances in materials chemistry, nanofabrication, and electronics. This is revealing scenarios from which synthetic enzymes can emerge, which were previously impossible, as well as interfaces with novel electrode materials. That means the control of the protein structure, electron transport pathway, and electrode surface can usher us into a new era of bioelectrochemistry. This article reviews the principle of electron transfer (ET) and considers how its application at the electrode, within the protein, and at a redox group is directing key advances in the understanding of protein structure to create systems that exhibit better efficiency and unique bioelectrochemistry.

  10. Protein (Viridiplantae): 308813231 [

    Lifescience Database Archive (English)

    Full Text Available XP_003083922.1 33090:9527 3041:5078 1035538:3664 13792:3664 70447:4128 70448:5494 Protein requir ... ed for actin cytoskeleton organization ... and cell cycle progression (ISS) Ostreococcus taur ...

  11. Protein (Viridiplantae): 308808566 [

    Lifescience Database Archive (English)

    Full Text Available XP_003081593.1 33090:6182 3041:4098 1035538:2508 13792:2508 70447:3211 70448:4097 Mitochondrial ... inheritance and actin cytoskeleton organization ... protein (ISS) Ostreococcus tauri MPPKKPPPPPPDAKSYP ...

  12. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  13. Protein (Viridiplantae): 255084748 [

    Lifescience Database Archive (English)

    Full Text Available XP_002504805.1 33090:7862 3041:6362 1035538:5159 13792:5159 38832:5340 296587:5427 DUF1244/molyb ... denum cofactor synthesis ... fusion protein Micromonas sp. RCC299 MASTRTEIEAYAF ...

  14. Protein (Viridiplantae): 303283029 [

    Lifescience Database Archive (English)

    Full Text Available XP_003060806.1 33090:7862 3041:6362 1035538:5159 13792:5159 38832:5340 38833:5093 564608:5093 mo ... lybdenum cofactor synthesis ... protein Micromonas pusilla CCMP1545 MVDAQTTEKIEAYA ...

  15. Protein (Viridiplantae): 308812183 [

    Lifescience Database Archive (English)

    Full Text Available XP_003083399.1 33090:12970 3041:5897 1035538:4613 13792:4613 70447:1628 70448:5196 Glycosylphosp ... hatidylinositol anchor synthesis ... protein (ISS) Ostreococcus tauri MSARRASFQSRFNDSSQ ...

  16. Protein (Viridiplantae): 308810647 [

    Lifescience Database Archive (English)

    Full Text Available XP_003082632.1 33090:15674 3041:5296 1035538:3911 13792:3911 70447:3635 70448:4717 senescence-in ... ducible chloroplast stay-green ... protein (ISS) Ostreococcus tauri MDRATTSSRASTARTFH ...

  17. Protein (Viridiplantae): 308811905 [

    Lifescience Database Archive (English)

    Full Text Available XP_003083260.1 33090:255 3041:4962 1035538:3528 13792:3528 70447:3840 70448:5111 T08009 probable ... ribosomal protein L5-green ... alga (ISS) Ostreococcus tauri MGKRRQKRKSQSVAKTTAYQ ...

  18. Protein (Cyanobacteria): 28423 [

    Lifescience Database Archive (English)

    Full Text Available ZP_10226597.1 1117:517 1118:7626 1125:2051 1160279:627 Type 4 prepilin-like proteins leader ... pept ... ide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis sp. T ...

  19. Protein (Cyanobacteria): 360784 [

    Lifescience Database Archive (English)

    Full Text Available YP_007097029.1 1117:17211 1118:17546 217161:1718 1173032:1718 1173020:1718 putative stress ... prote ... in (general stress ... protein 26) Chamaesiphon minutus PCC 6605 MANATENQ ...

  20. Protein (Cyanobacteria): 392180 [

    Lifescience Database Archive (English)

    Full Text Available ZP_07113914.1 1117:24513 1150:7038 1158:3915 272129:3709 Bifunctional protein birA (Includes: Biotin ... otin operon repressor; Biotin --(acetyl-CoA-carboxylase) synthetase (Biotin --prot ...

  1. Interactive protein manipulation

    Energy Technology Data Exchange (ETDEWEB)

    SNCrivelli@lbl.gov

    2003-07-01

    We describe an interactive visualization and modeling program for the creation of protein structures ''from scratch''. The input to our program is an amino acid sequence -decoded from a gene- and a sequence of predicted secondary structure types for each amino acid-provided by external structure prediction programs. Our program can be used in the set-up phase of a protein structure prediction process; the structures created with it serve as input for a subsequent global internal energy minimization, or another method of protein structure prediction. Our program supports basic visualization methods for protein structures, interactive manipulation based on inverse kinematics, and visualization guides to aid a user in creating ''good'' initial structures.

  2. Protein (Viridiplantae): 308811366 [

    Lifescience Database Archive (English)

    Full Text Available XP_003082991.1 33090:1951 3041:1340 1035538:592 13792:592 70447:610 70448:205 Transporter, ABC s ... uperfamily (Breast cancer ... resistance protein) (ISS), partial Ostreococcus ta ...

  3. Protein (Viridiplantae): 308810513 [

    Lifescience Database Archive (English)

    Full Text Available XP_003082565.1 33090:8864 3041:8803 1035538:7822 13792:7822 70447:3615 70448:4680 Predicted memb ... rane protein (associated with esophageal cancer ... in humans) (ISS) Ostreococcus tauri MTSSRKLCAFVRDA ...

  4. Protein (Viridiplantae): 308804289 [

    Lifescience Database Archive (English)

    Full Text Available XP_003079457.1 33090:1951 3041:1340 1035538:592 13792:592 70447:610 70448:205 Transporter, ABC s ... uperfamily (Breast cancer ... resistance protein) (ISS) Ostreococcus tauri MASRV ...

  5. Untying knots in proteins.

    Science.gov (United States)

    Sułkowska, Joanna I; Sułkowski, Piotr; Szymczak, Piotr; Cieplak, Marek

    2010-10-13

    A shoelace can be readily untied by pulling its ends rather than its loops. Attempting to untie a native knot in a protein can also succeed or fail depending on where one pulls. However, thermal fluctuations induced by the surrounding water affect conformations stochastically and may add to the uncertainty of the outcome. When the protein is pulled by the termini, the knot can only get tightened, and any attempt at untying results in failure. We show that, by pulling specific amino acids, one may easily retract a terminal segment of the backbone from the knotting loop and untangle the knot. At still other amino acids, the outcome of pulling can go either way. We study the dependence of the untying probability on the way the protein is grasped, the pulling speed, and the temperature. Elucidation of the mechanisms underlying this dependence is critical for a successful experimental realization of protein knot untying. PMID:20857930

  6. Protein (Viridiplantae): 308806666 [

    Lifescience Database Archive (English)

    Full Text Available XP_003080644.1 33090:21099 3041:5360 1035538:3986 13792:3986 70447:3049 70448:3532 COG3310: Unch ... aracterized protein conserved in bacteria ... (ISS) Ostreococcus tauri MRRTCASRNLARSPVAARERCRQMV ...

  7. Protein (Viridiplantae): 308803575 [

    Lifescience Database Archive (English)

    Full Text Available XP_003079100.1 33090:20519 3041:4460 1035538:2940 13792:2940 70447:2035 70448:2555 COG4399: Unch ... aracterized protein conserved in bacteria ... (ISS) Ostreococcus tauri MKALQRLVLRGSTDGVRPACERAMA ...

  8. Protein (Viridiplantae): 308804123 [

    Lifescience Database Archive (English)

    Full Text Available XP_003079374.1 33090:20519 3041:4460 1035538:2940 13792:2940 70447:2035 70448:2555 COG4399: Unch ... aracterized protein conserved in bacteria ... (ISS) Ostreococcus tauri MDSLATSRRRRLARAGAAIATALAL ...

  9. Protein (Viridiplantae): 255077633 [

    Lifescience Database Archive (English)

    Full Text Available XP_002502450.1 33090:20956 3041:5145 1035538:3740 13792:3740 38832:3722 296587:3525 isocitrate d ... ehydrogenase (NADP+), bacteria -like protein Micromonas sp. RCC299 MAAASAGGKIQAAPM ...

  10. Protein (Cyanobacteria): 228257 [

    Lifescience Database Archive (English)

    Full Text Available ZP_09784859.1 1117:4333 1150:1533 35823:3512 376219:3411 Protein ushA precursor (Includes: UDP-sugar ... ugar hydrolase (UDP-sugar ... pyrophosphatase) (UDP-sugar ... diphosphatase); 5'-nuc ...

  11. Protein folding and cosmology

    CERN Document Server

    González-Diáz, P F

    1997-01-01

    Protein denaturing induced by supercooling is interpreted as a process where some or all internal symmetries of the native protein are spontaneously broken. Hence, the free-energy potential corresponding to a folding-funnel landscape becomes temperature-dependent and describes a phase transition. The idea that deformed vortices could be produced in the transition induced by temperature quenching, from native proteins to unfolded conformations is discussed in terms of the Zurek mechanism that implements the analogy between vortices, created in the laboratory at low energy, and the cosmic strings which are thought to have been left after symmetry breaking phase transitions in the early universe. An experiment is proposed to test the above idea which generalizes the cosmological analogy to also encompass biological systems and push a step ahead the view that protein folding is a biological equivalent of the big bang.

  12. Protein (Viridiplantae): 308804764 [

    Lifescience Database Archive (English)

    Full Text Available XP_003079694.1 33090:24290 3041:9393 1035538:8433 13792:8433 70447:5209 70448:2928 probable memb ... rane protein YCR013c-yeast ... (ISS) Ostreococcus tauri MQLREVKERLRAYFSSSAATPGRTR ...

  13. Protein (Cyanobacteria): 338848 [

    Lifescience Database Archive (English)

    Full Text Available YP_007172477.1 1117:11758 1118:7408 13034:1671 292566:1671 13035:1671 cell envelope-related func ... tion transcriptional attenuator ... common domain protein Dactylococcopsis salina PCC ...

  14. Electron transfer in proteins

    DEFF Research Database (Denmark)

    Farver, O; Pecht, I

    1991-01-01

    Electron migration between and within proteins is one of the most prevalent forms of biological energy conversion processes. Electron transfer reactions take place between active centers such as transition metal ions or organic cofactors over considerable distances at fast rates and with remarkable...... specificity. The electron transfer is attained through weak electronic interaction between the active sites, so that considerable research efforts are centered on resolving the factors that control the rates of long-distance electron transfer reactions in proteins. These factors include (in addition to the......-containing proteins. These proteins serve almost exclusively in electron transfer reactions, and as it turns out, their metal coordination sites are endowed with properties uniquely optimized for their function....

  15. Protein Colloidal Aggregation Project

    Science.gov (United States)

    Oliva-Buisson, Yvette J. (Compiler)

    2014-01-01

    To investigate the pathways and kinetics of protein aggregation to allow accurate predictive modeling of the process and evaluation of potential inhibitors to prevalent diseases including cataract formation, chronic traumatic encephalopathy, Alzheimer's Disease, Parkinson's Disease and others.

  16. Interactive protein manipulation

    International Nuclear Information System (INIS)

    We describe an interactive visualization and modeling program for the creation of protein structures ''from scratch''. The input to our program is an amino acid sequence -decoded from a gene- and a sequence of predicted secondary structure types for each amino acid-provided by external structure prediction programs. Our program can be used in the set-up phase of a protein structure prediction process; the structures created with it serve as input for a subsequent global internal energy minimization, or another method of protein structure prediction. Our program supports basic visualization methods for protein structures, interactive manipulation based on inverse kinematics, and visualization guides to aid a user in creating ''good'' initial structures

  17. Egg protein hydrolysates

    NARCIS (Netherlands)

    Amerongen, van A.; Beelen, M.J.C.; Wolbers, L.A.M.; Gilst, van W.H.; Buikema, J.H.; Nelissen, J.W.P.M.

    2009-01-01

    The present invention provides egg-protein hydrolysates with DPP-IV inhibitory activity which are particularly suited for the treatment of diabetes. Particularly advantageous is to use hydrolysate of lysozyme for the treatment of diabetes.

  18. Bence-Jones protein - quantitative

    Science.gov (United States)

    Immunoglobulin light chains - urine; Urine Bence-Jones protein ... Bence-Jones proteins are a part of regular antibodies called light chains. These proteins are not normally in urine. Sometimes, when ...

  19. The Malignant Protein Puzzle.

    Science.gov (United States)

    Walker, Lary C; Jucker, Mathias

    2016-01-01

    When most people hear the words malignant and brain, cancer immediately comes to mind. But our authors argue that proteins can be malignant too, and can spread harmfully through the brain in neurodegenerative diseases that include Alzheimer's, Parkinson's, CTE, and ALS. Studying how proteins such as PrP, amyloid beta, tau, and others aggregate and spread, and kill brain cells, represents a crucial new frontier in neuroscience. PMID:27408676

  20. Fish protein hydrolysates

    Energy Technology Data Exchange (ETDEWEB)

    Mackie, I.M.

    1982-01-01

    Proteolytic enzymes now available in commercial quantities can be used to liquefy the fish and fish waste presently considered suitable for conversion to fish meal. The products obtained are readily dispersed or dissolved in water and have a high nutritional value. They have been satisfactorily used as substitutes for milk proteins in milk replacers for young animals. Further research is necessary on means of controlling the degree of hydrolysis to give protein preparations with acceptable functional properties as human food supplements. (Refs. 21).

  1. Recombinant Collagenlike Proteins

    Science.gov (United States)

    Fertala, Andzej

    2007-01-01

    A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, "Synthesis of human procollagens and collagens in recombinant DNA systems." Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications. Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.

  2. Untying Knots in Proteins

    OpenAIRE

    Sułkowska, Joanna I.; Sułkowski, Piotr; Szymczak, Piotr; Cieplak, Marek

    2010-01-01

    A shoelace can be readily untied by pulling its ends rather than its loops. Attempting to untie a native knot in a protein can also succeed or fail depending on where one pulls. However, thermal fluctuations induced by the surrounding water affect conformations stochastically and may add to the uncertainty of the outcome. When the protein is pulled by the termini, the knot can only get tightened, and any attempt at untying results in failure. We show that, by pulling specific amino acids, ...

  3. Digestibility of sorghum proteins.

    OpenAIRE

    Axtell, J D; Kirleis, A. W.; Hassen, M M; D'Croz Mason, N; Mertz, E T; Munck, L.

    1981-01-01

    Published information indicates that rice, maize, and wheat proteins are much more digestible in children than sorghum proteins are (66-81% compared with 46%). However, this digestibility difference cannot be demonstrated with the weanling rat, which gave digestibility values of 80% for cooked and 85% for uncooked sorghum gruels. Therefore, a search was made for a laboratory system sensitive to the digestibility differences between sorghum and other cereals. We found that porcine pepsin in vi...

  4. Identifying Unknown Proteins

    OpenAIRE

    Barker, Winona C.; Dayhoff, Margaret O.

    1983-01-01

    In this paper we discuss ways to identify a protein, both when its amino acid sequence is known and, particularly, prior to the determination of the complete sequence. If a similar sequence is in the Protein Sequence Database, an unknown may be identified on the basis of partial or ambiguous sequence data, or on the basis of amino acid composition. Identification in the early stages of structural determination can save time and scarce resources by preventing duplicate effort or by suggesting ...

  5. Proteins and their crystals

    Czech Academy of Sciences Publication Activity Database

    Kutá-Smatanová, Ivana; Hogg, T.; Hilgenfeld, R.; Grandori, R.; Carey, J.; Vácha, František; Štys, Dalibor

    2003-01-01

    Roč. 10, č. 1 (2003), s. 31-32. ISSN 1211-5894 R&D Projects: GA MŠk LN00A141; GA ČR GA206/00/D007 Institutional research plan: CEZ:AV0Z5051902; CEZ:MSM 123100001 Keywords : pokeweed antiviral protein * flavodoxin-like protein * PSII Subject RIV: EB - Genetics ; Molecular Biology

  6. Occupational protein contact dermatitis.

    Science.gov (United States)

    Barbaud, Annick; Poreaux, Claire; Penven, Emmanuelle; Waton, Julie

    2015-12-01

    Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very low concentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals. PMID:26242922

  7. Protein hydrolysates in sports nutrition

    Directory of Open Access Journals (Sweden)

    Manninen Anssi H

    2009-09-01

    Full Text Available Abstract It has been suggested that protein hydrolysates providing mainly di- and tripeptides are superior to intact (whole proteins and free amino acids in terms of skeletal muscle protein anabolism. This review provides a critical examination of protein hydrolysate studies conducted in healthy humans with special reference to sports nutrition. The effects of protein hydrolysate ingestion on blood amino acid levels, muscle protein anabolism, body composition, exercise performance and muscle glycogen resynthesis are discussed.

  8. Protein Functionality in Food Systems

    Institute of Scientific and Technical Information of China (English)

    WANG Panpan

    2010-01-01

    The structure,shape,color,smell and taste of food were decided by protein functionality.The utilization of protein will improve by changing the protein functionality.Protein functionality is also advantage to maintain and utilize the nutrition of food.This paper summarized the nature,classification,factors and prospect of protein functionality.It ccn provide a theoretical basis for application of protein in food industry.

  9. Protein Databases on the Internet

    OpenAIRE

    Xu, Dong

    2004-01-01

    Protein databases have become a crucial part of modern biology. Huge amounts of data for protein structures, functions, and particularly sequences are being generated. Searching databases is often the first step in the study of a new protein. Comparison between proteins or between protein families provides information about the relationship between proteins within a genome or across different species, and hence offers much more information than can be obtained by studying only an isolated pro...

  10. More protein in cereals?

    International Nuclear Information System (INIS)

    Ways in which the protein content of plant crops may be raised by the use of nuclear radiation are to be discussed at a symposium in Vienna in June next year, organized by the joint Food and Agriculture Organization/Agency Division of Atomic Energy in Food and Agriculture. Plant crops - especially cereal grains - are the basic food and protein source of most of the world's population, particularly in less-developed countries. But their natural protein content is low; increasing the quantity and nutritional quality of plant protein is potentially the most feasible way to combat widespread protein malnutrition. This improvement in seed stock can be achieved by plant breeding methods in which nuclear irradiation techniques are used to induce mutations in grain, and other isotopic techniques can be used to select only those mutants which have the desired properties. The scientists who attend the symposium will have an opportunity to review what mutation plant breeders have achieved, the application of nuclear techniques to screening for protein and amino-acid content and nutritional value, and isotopic methods which contribute to research in plant nutrition and physiology. (author)

  11. Stretching to Understand Proteins

    Science.gov (United States)

    Cieplak, Marek

    2007-03-01

    Mechanical stretching of single proteins has been studied experimentally for about 50 proteins yielding a variety of force patterns and values of the peak forces. We have performed a theoretical survey of 7749 proteins of known native structure and map out the landscape of possible dynamical behaviors unders stretching at constant speed. The model used is constructed based on the native geometry. It is solved by methods of molecular dynamics and validated by comparing the theoretical predictions to experimental results. We characterize the distribution of peak forces and on correlations with the system size and with the structure classification as characterized by the CATH scheme. We identify proteins with the biggest forces and show that they belong to few topology classes. We determine which protein segments act as mechanical clamps and show that, in most cases, they correspond to long stretches of parallel beta-strands, but other mechanisms are also possible. We then consider stretching by fluid flows. We show that unfolding induced by a uniform flow shows a richer behavior than that in the force clamp. The dynamics of unfolding is found to depend strongly on the selection of the amino acid, usually one of the termini, which is anchored. These features offer potentially wider diagnostic tools to investigate structure of proteins compared to experiments based on the atomic force microscopy.

  12. Inferring protein function by domain context similarities in protein-protein interaction networks

    OpenAIRE

    Sun Zhirong; Liu Ke; Chen Hu; Zhang Song

    2009-01-01

    Abstract Background Genome sequencing projects generate massive amounts of sequence data but there are still many proteins whose functions remain unknown. The availability of large scale protein-protein interaction data sets makes it possible to develop new function prediction methods based on protein-protein interaction (PPI) networks. Although several existing methods combine multiple information resources, there is no study that integrates protein domain information and PPI networks to pre...

  13. ADSORPTION OF PROTEIN ON NANOPARTICLES

    Institute of Scientific and Technical Information of China (English)

    WU Qi

    1994-01-01

    The adsorption of protein on nanoparticles was studied by using dynamic light scattering to measure the hydrodynamic size of both pure protein and nanoparticles adsorbed with different amounts of protein. The thickness of the adsorbed protein layer increases as protein concentration, but decreases as the initial size of nanoparticles. After properly scaling the thickness with the initial diameter, we are able to fit all experimental data with a single master curve. Our experimental results suggest that the adsorbed proteins form a monolayeron the nanoparticle surface and the adsorbed protein molecules are attached to the particle surface at many points through a possible hydrogen-bonding. Our results also indicate that as protein concentration increases, the overall shape of the adsorbed protein molecule continuously changes from a flat layer on the particle surface to a stretched coil extended into water. During the change, the hydrodynamic volume of the adsorbed protein increases linearly with protein concentration.

  14. Measuring protein breakdown rate in individual proteins in vivo

    DEFF Research Database (Denmark)

    Holm, Lars; Kjaer, Michael

    2010-01-01

    To outline different approaches of how protein breakdown can be quantified and to present a new approach to determine the fractional breakdown rate of individual slow turnover proteins in vivo.......To outline different approaches of how protein breakdown can be quantified and to present a new approach to determine the fractional breakdown rate of individual slow turnover proteins in vivo....

  15. Histophilus somni Surface Proteins.

    Science.gov (United States)

    Corbeil, Lynette B

    2016-01-01

    The pathogen surface is usually the first site of interaction with the host. Histophilus somni was earlier thought to only have an outer membrane on its surface. Now it is known that the surface is composed of many virulence factors, including outer membrane proteins, lipooligosaccharide or endotoxin, a fibrillar network, and an exopolysaccharide. Outer membrane blebs, endotoxin, the fibrillar network, and the exopolysaccharide are also shed from the surface. This review will focus on the surface proteins of this pathogen that may colonize the mucosal surface of ruminants as a commensal or may cause pneumonia, septicemia, myocarditis, thrombotic meningoencephalitis, arthritis, and/or abortion. The major outer membrane protein has been well studied. Since its size and epitopes vary from strain to strain, it may be useful for typing strains. Iron-regulated OMPs have also received much attention because of their role in iron uptake for in vivo growth of H. somni. Other OMPs may be protective, based on passive immunization with monospecific antibodies and active immunization experiments. The surface and shed fibrillar network has been shown to be an immunoglobulin-binding protein in that it binds bovine IgG2 by the Fc portion. Two repeat domains (DR1 and DR2) have cytotoxic Fic motifs. Vaccine studies with recombinant DR2 are promising. Studies of the bacterial genome as well as comparison of surface proteins of different strains from the various H. somni syndromes and carrier states will be discussed and have provided much insight into pathogenesis and protection. PMID:26728061

  16. Ontology integration to identify protein complex in protein interaction networks

    OpenAIRE

    Yang Zhihao; Lin Hongfei; Xu Bo

    2011-01-01

    Abstract Background Protein complexes can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of protein complexes detection algorithms. Methods We have developed novel semantic similarity metho...

  17. Identifying Protein-Protein Interaction Sites Using Covering Algorithm

    OpenAIRE

    Jie Song; Jiaxing Cheng; Xiuquan Du

    2009-01-01

    Identification of protein-protein interface residues is crucial for structural biology. This paper proposes a covering algorithm for predicting protein-protein interface residues with features including protein sequence profile and residue accessible area. This method adequately utilizes the characters of a covering algorithm which have simple, lower complexity and high accuracy for high dimension data. The covering algorithm can achieve a comparable performance (69.62%, Complete dataset; 60....

  18. Protein-Protein Interaction Detection: Methods and Analysis

    OpenAIRE

    V. Srinivasa Rao; Srinivas, K.; Sujini, G. N.; G. N. Sunand Kumar

    2014-01-01

    Protein-protein interaction plays key role in predicting the protein function of target protein and drug ability of molecules. The majority of genes and proteins realize resulting phenotype functions as a set of interactions. The in vitro and in vivo methods like affinity purification, Y2H (yeast 2 hybrid), TAP (tandem affinity purification), and so forth have their own limitations like cost, time, and so forth, and the resultant data sets are noisy and have more false positives to annotate t...

  19. Protein Microarray On-Demand: A Novel Protein Microarray System

    OpenAIRE

    Chatterjee, Deb K.; Sitaraman, Kalavathy; Baptista, Cassio; Hartley, James; Hill, Thomas M.; David J. Munroe

    2008-01-01

    We describe a novel, simple and low-cost protein microarray strategy wherein the microarrays are generated by printing expression ready plasmid DNAs onto slides that can be converted into protein arrays on-demand. The printed expression plasmids serve dual purposes as they not only direct the synthesis of the protein of interest; they also serve to capture the newly synthesized proteins through a high affinity DNA-protein interaction. To accomplish this we have exploited the high-affinity bin...

  20. Polarizable protein packing

    KAUST Repository

    Ng, Albert H.

    2011-01-24

    To incorporate protein polarization effects within a protein combinatorial optimization framework, we decompose the polarizable force field AMOEBA into low order terms. Including terms up to the third-order provides a fair approximation to the full energy while maintaining tractability. We represent the polarizable packing problem for protein G as a hypergraph and solve for optimal rotamers with the FASTER combinatorial optimization algorithm. These approximate energy models can be improved to high accuracy [root mean square deviation (rmsd) < 1 kJ mol -1] via ridge regression. The resulting trained approximations are used to efficiently identify new, low-energy solutions. The approach is general and should allow combinatorial optimization of other many-body problems. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011 Copyright © 2011 Wiley Periodicals, Inc.

  1. Polarizable protein packing.

    Science.gov (United States)

    Ng, Albert H; Snow, Christopher D

    2011-05-01

    To incorporate protein polarization effects within a protein combinatorial optimization framework, we decompose the polarizable force field AMOEBA into low order terms. Including terms up to the third-order provides a fair approximation to the full energy while maintaining tractability. We represent the polarizable packing problem for protein G as a hypergraph and solve for optimal rotamers with the FASTER combinatorial optimization algorithm. These approximate energy models can be improved to high accuracy [root mean square deviation (rmsd) < 1 kJ mol(-1)] via ridge regression. The resulting trained approximations are used to efficiently identify new, low-energy solutions. The approach is general and should allow combinatorial optimization of other many-body problems. PMID:21264879

  2. Electron transfer in proteins.

    Science.gov (United States)

    Gray, H B; Winkler, J R

    1996-01-01

    Electron-transfer (ET) reactions are key steps in a diverse array of biological transformations ranging from photosynthesis to aerobic respiration. A powerful theoretical formalism has been developed that describes ET rates in terms of two parameters: the nuclear reorganization energy (lambda) and the electronic-coupling strength (HAB). Studies of ET reactions in ruthenium-modified proteins have probed lambda and HAB in several metalloproteins (cytochrome c, myoglobin, azurin). This work has shown that protein reorganization energies are sensitive to the medium surrounding the redox sites and that an aqueous environment, in particular, leads to large reorganization energies. Analyses of electronic-coupling strengths suggest that the efficiency of long-range ET depends on the protein secondary structure: beta sheets appear to mediate coupling more efficiently than alpha-helical structures, and hydrogen bonds play a critical role in both. PMID:8811189

  3. Accessory Proteins at ERES

    DEFF Research Database (Denmark)

    Klinkenberg, Rafael David

    proteins. Together these components co‐operate in cargo‐selection as well as forming, loading and releasing budding vesicles from specific regions on the membrane surface of the ER. Coat components furthermore convey vesicle targeting towards the Golgi. However, not much is known about the mechanisms that...... regulate the COPII assembly at the vesicle bud site. This thesis provides the first regulatory mechanism of COPII assembly in relation to ER‐membrane lipid‐signal recognition by the accessory protein p125A (Sec23IP). The aim of the project was to characterize p125A function by dissecting two main domains...... in the protein; a putative lipid‐associating domain termed the DDHD domain that is defined by the four amino acid motif that gives the domain its name; and a ubiquitously found domain termed Sterile α‐motif (SAM), which is mostly associated with oligomerization and polymerization. We first show, that...

  4. Sound of proteins

    DEFF Research Database (Denmark)

    2007-01-01

    In my group we work with Molecular Dynamics to model several different proteins and protein systems. We submit our modelled molecules to changes in temperature, changes in solvent composition and even external pulling forces. To analyze our simulation results we have so far used visual inspection...... and statistical analysis of the resulting molecular trajectories (as everybody else!). However, recently I started assigning a particular sound frequency to each amino acid in the protein, and by setting the amplitude of each frequency according to the movement amplitude we can "hear" whenever two aminoacids....... These are early days, and it still remains to be proven that this method has any advantage over other methods, but at least it is fun to do and the harmonies produced invoke an eerie sounding futuristic landscape...

  5. Ubiquitin domain proteins in disease

    DEFF Research Database (Denmark)

    Klausen, Louise Kjær; Schulze, Andrea; Seeger, Michael;

    2007-01-01

    The human genome encodes several ubiquitin-like (UBL) domain proteins (UDPs). Members of this protein family are involved in a variety of cellular functions and many are connected to the ubiquitin proteasome system, an essential pathway for protein degradation in eukaryotic cells. Despite their...... and cancer. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com)....

  6. SOY PROTEIN NANOPARTICLES AND NANOCOMPOSITES

    Science.gov (United States)

    Soy protein isolate (SPI) is obtained from soybean by removing soybean oil and soy carbohydrates. SPI contains more than 90% protein. Structurally, SPI is a globular protein and its aggregates in water consist of sphere-like protein particles. The number average aggregate size of SPI at pH=5.2 is...

  7. The Formation of Protein Structure

    DEFF Research Database (Denmark)

    Bohr, Jakob; Bohr, Henrik; Brunak, Søren

    1996-01-01

    Dynamically induced curvature owing to long-range excitations along the backbones of protein molecules with non-linear elastic properties may control the folding of proteins.......Dynamically induced curvature owing to long-range excitations along the backbones of protein molecules with non-linear elastic properties may control the folding of proteins....

  8. Vibrational spectroscopy of proteins

    International Nuclear Information System (INIS)

    Two important steps for the development of a biosensor are the immobilization of the biological component (e.g. protein) on a surface and the enhancement of the signal to improve the sensitivity of detection. To address these subjects, the present work describes Fourier transform infrared (FTIR) investigations of several proteins bound to the surface of an attenuated total reflection (ATR) crystal. Furthermore, new nanostructured surfaces for signal enhancement were developed for use in FTIR microscopy. The mitochondrial redox-protein cytochrome c oxidase (CcO) was incorporated into a protein-tethered bilayer lipid membrane (ptBLM) on an ATR crystal featuring a roughened two-layer gold surface for signal enhancement. Electrochemical excitation by periodic potential pulses at different modulation frequencies was followed by time-resolved FTIR spectroscopy. Phase sensitive detection was used for deconvolution of the IR spectra into vibrational components. A model based on protonation-dependent chemical reaction kinetics could be fitted to the time evolution of IR bands attributed to several different redox centers of the CcO. Further investigations involved the odorant binding protein 14 (OBP14) of the honey bee (Apis mellifera), which was studied using ATR-FTIR spectroscopy and circular dichroism. OBP14 was found to be thermally stable up to 45 °C, thus permitting the potential application of this protein for the fabrication of biosensors. Thermal denaturation measurements showed that odorant binding increases the thermal stability of the OBP-odorant complex. In another project, plasmonic nanostructures were fabricated that enhance the absorbance in FTIR microscopy measurements. The nanostructures are composed of an array of round-shaped insulator and gold discs on top of a continuous gold layer. Enhancement factors of up to ⁓125 could be observed with self-assembled monolayers of dodecanethiol molecules immobilized on the gold surface (author)

  9. Modeling Mercury in Proteins.

    Science.gov (United States)

    Parks, J M; Smith, J C

    2016-01-01

    Mercury (Hg) is a naturally occurring element that is released into the biosphere both by natural processes and anthropogenic activities. Although its reduced, elemental form Hg(0) is relatively nontoxic, other forms such as Hg(2+) and, in particular, its methylated form, methylmercury, are toxic, with deleterious effects on both ecosystems and humans. Microorganisms play important roles in the transformation of mercury in the environment. Inorganic Hg(2+) can be methylated by certain bacteria and archaea to form methylmercury. Conversely, bacteria also demethylate methylmercury and reduce Hg(2+) to relatively inert Hg(0). Transformations and toxicity occur as a result of mercury interacting with various proteins. Clearly, then, understanding the toxic effects of mercury and its cycling in the environment requires characterization of these interactions. Computational approaches are ideally suited to studies of mercury in proteins because they can provide a detailed molecular picture and circumvent issues associated with toxicity. Here, we describe computational methods for investigating and characterizing how mercury binds to proteins, how inter- and intraprotein transfer of mercury is orchestrated in biological systems, and how chemical reactions in proteins transform the metal. We describe quantum chemical analyses of aqueous Hg(II), which reveal critical factors that determine ligand-binding propensities. We then provide a perspective on how we used chemical reasoning to discover how microorganisms methylate mercury. We also highlight our combined computational and experimental studies of the proteins and enzymes of the mer operon, a suite of genes that confer mercury resistance in many bacteria. Lastly, we place work on mercury in proteins in the context of what is needed for a comprehensive multiscale model of environmental mercury cycling. PMID:27497164

  10. Mining protein structure data

    OpenAIRE

    Santos, José Carlos Almeida

    2006-01-01

    The principal topic of this work is the application of data mining techniques, in particular of machine learning, to the discovery of knowledge in a protein database. In the first chapter a general background is presented. Namely, in section 1.1 we overview the methodology of a Data Mining project and its main algorithms. In section 1.2 an introduction to the proteins and its supporting file formats is outlined. This chapter is concluded with section 1.3 which defines that main problem we...

  11. Protein-based ferrogels.

    Science.gov (United States)

    Mody, Puja; Hart, Cassidy; Romano, Siena; El-Magbri, Mariam; Esson, Moira M; Ibeh, Trisha; Knowlton, Elizabeth D; Zhang, Ming; Wagner, Michael J; Hartings, Matthew R

    2016-06-01

    We present a novel synthesis in which hemoglobin and Fe(2+) react, in the presence of KNO3 and KOH, to produce protein microgels that contain magnetic iron oxide nanoparticles. The synthesis results in microgels with polymer properties (denaturing and glass transition temperatures) that are consistent with the dried protein. The iron oxide nanoparticles that exhibit an average diameter of 22nm, are ferrimagnetic, and display properties consistent with Fe3O4. The multiple functional capabilities displayed by these materials: biocompatibility, magnetism, dye uptake and controlled release, and other properties archetypal of hydrogels, will make the magnetic hydrogels attractive for a number of biomedical applications. PMID:26901627

  12. Lipid-transfer proteins.

    Science.gov (United States)

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Ye, Xiujuan

    2012-01-01

    Lipid-transfer proteins (LTPs) are basic proteins found in abundance in higher plants. LTPs play lots of roles in plants such as participation in cutin formation, embryogenesis, defense reactions against phytopathogens, symbiosis, and the adaptation of plants to various environmental conditions. In addition, LTPs from field mustard and Chinese daffodil exhibit antiproliferative activity against human cancer cells. LTPs from chili pepper and coffee manifest inhibitory activity against fungi pathogenic to humans such as Candida species. The intent of this article is to review LTPs in the plant kingdom. PMID:23193591

  13. Chirality and Protein Folding

    OpenAIRE

    Kwiecinska, Joanna I.; Cieplak, Marek

    2004-01-01

    There are several simple criteria of folding to a native state in model proteins. One of them involves crossing of a threshold value of the RMSD distance away from the native state. Another checks whether all native contacts are established, i.e. whether the interacting amino acids come closer than some characteristic distance. We use Go-like models of proteins and show that such simple criteria may prompt one to declare folding even though fragments of the resulting conformations have a wron...

  14. Conformation Distributions in Adsorbed Proteins.

    Science.gov (United States)

    Meuse, Curtis W.; Hubbard, Joseph B.; Vrettos, John S.; Smith, Jackson R.; Cicerone, Marcus T.

    2007-03-01

    While the structural basis of protein function is well understood in the biopharmaceutical and biotechnology industries, few methods for the characterization and comparison of protein conformation distributions are available. New methods capable of measuring the stability of protein conformations and the integrity of protein-protein, protein-ligand and protein-surface interactions both in solution and on surfaces are needed to help the development of protein-based products. We are developing infrared spectroscopy methods for the characterization and comparison of molecular conformation distributions in monolayers and in solutions. We have extracted an order parameter describing the orientational and conformational variations of protein functional groups around the average molecular values from a single polarized spectrum. We will discuss the development of these methods and compare them to amide hydrogen/deuterium exchange methods for albumin in solution and on different polymer surfaces to show that our order parameter is related to protein stability.

  15. G Protein-coupled receptors

    OpenAIRE

    Ross, Elliott M.

    2014-01-01

    G protein-coupled receptors and heterotrimeric G proteins can diffuse laterally in the plasma membrane such that one receptor can catalyze the activation (GDP/GTP exchange) of multiple G proteins. In some cases, these processes are fast enough to support molecular signal amplification, where a single receptor maintains the activation of multiple G proteins at steady-state. Amplification in cells is probably highly regulated. It depends upon the identities of the G receptor and G protein - som...

  16. Protein stability, flexibility and function

    DEFF Research Database (Denmark)

    Teilum, Kaare; Olsen, Johan G; Kragelund, Birthe B

    2011-01-01

    Proteins rely on flexibility to respond to environmental changes, ligand binding and chemical modifications. Potentially, a perturbation that changes the flexibility of a protein may interfere with its function. Millions of mutations have been performed on thousands of proteins in quests for a...... data presented is it clear that there are specific sites (flexibility hotspots) in proteins that are important for both binding and stability. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches....

  17. Protein oxidation in aquatic foods

    DEFF Research Database (Denmark)

    Baron, Caroline P.

    oxidation. The protein carbonyl group measurement is the widely used method for estimating protein oxidation in foods and has been used in fish muscle. The chapter also talks about the impact of protein oxidation on protein functionality, fish muscle texture, and food nutritional value. Protein oxidation...... may not only induce quality losses but may be desirable in some type of foods, such as salted herring....

  18. Measuring protein breakdown in individual proteins in vivo

    DEFF Research Database (Denmark)

    Holm, Lars; Kjær, Michael

    2010-01-01

    PURPOSE OF REVIEW: To outline different approaches of how protein breakdown can be quantified and to present a new approach to determine the fractional breakdown rate of individual slow turnover proteins in vivo. RECENT FINDINGS: None of the available methods for determining protein breakdown can...... be used to determine the breakdown rate of specific proteins and, therefore, do not keep up to the preceding methodological demands in physiological research. A newly developed approach to determine the fractional breakdown rate of single proteins seems promising. Its conceptual advantage is that the...... proteins of interest are the site of measurement. Hence, the application initially demands the proteins to be labeled with stable isotopically labeled amino acids. Subsequently, the loss of label from the proteins will be dependent on the protein breakdown rate when no labeled amino acids are...

  19. Integral UBL domain proteins: a family of proteasome interacting proteins

    DEFF Research Database (Denmark)

    Hartmann-Petersen, Rasmus; Gordon, Colin

    2004-01-01

    The family of ubiquitin-like (UBL) domain proteins (UDPs) comprises a conserved group of proteins involved in a multitude of different cellular activities. However, recent studies on UBL-domain proteins indicate that these proteins appear to share a common property in their ability to interact with......-domain proteins catalyse the formation of ubiquitin-protein conjugates, whereas others appear to target ubiquitinated proteins for degradation and interact with chaperones. Hence, by binding to the 26S proteasome the UBL-domain proteins seem to tailor and direct the basic proteolytic functions of the particle to...... 26S proteasomes. The 26S proteasome is a multisubunit protease which is responsible for the majority of intracellular proteolysis in eukaryotic cells. Before degradation commences most proteins are first marked for destruction by being coupled to a chain of ubiquitin molecules. Some UBL...

  20. Interaction between plate make and protein in protein crystallisation screening.

    Directory of Open Access Journals (Sweden)

    Gordon J King

    Full Text Available BACKGROUND: Protein crystallisation screening involves the parallel testing of large numbers of candidate conditions with the aim of identifying conditions suitable as a starting point for the production of diffraction quality crystals. Generally, condition screening is performed in 96-well plates. While previous studies have examined the effects of protein construct, protein purity, or crystallisation condition ingredients on protein crystallisation, few have examined the effect of the crystallisation plate. METHODOLOGY/PRINCIPAL FINDINGS: We performed a statistically rigorous examination of protein crystallisation, and evaluated interactions between crystallisation success and plate row/column, different plates of same make, different plate makes and different proteins. From our analysis of protein crystallisation, we found a significant interaction between plate make and the specific protein being crystallised. CONCLUSIONS/SIGNIFICANCE: Protein crystal structure determination is the principal method for determining protein structure but is limited by the need to produce crystals of the protein under study. Many important proteins are difficult to crystallize, so that identification of factors that assist crystallisation could open up the structure determination of these more challenging targets. Our findings suggest that protein crystallisation success may be improved by matching a protein with its optimal plate make.

  1. HIV protein sequence hotspots for crosstalk with host hub proteins.

    Directory of Open Access Journals (Sweden)

    Mahdi Sarmady

    Full Text Available HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2. We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes.

  2. Characterization of Protein Complexes and Subcomplexes in Protein-Protein Interaction Databases

    OpenAIRE

    Nazar Zaki; Elfadil A. Mohamed; Antonio Mora

    2015-01-01

    The identification and characterization of protein complexes implicated in protein-protein interaction data are crucial to the understanding of the molecular events under normal and abnormal physiological conditions. This paper provides a novel characterization of subcomplexes in protein interaction databases, stressing definition and representation issues, quantification, biological validation, network metrics, motifs, modularity, and gene ontology (GO) terms. The paper introduces the concep...

  3. Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

    Directory of Open Access Journals (Sweden)

    Peiqiang Yu

    2007-01-01

    Full Text Available The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behavior and nutrient utilization and availability. The emphasis of this review was on (1 using the newly advanced synchrotron technology (S-FTIR as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2 revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3 prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4 obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.

  4. Transient protein-protein interactions visualized by solution NMR.

    Science.gov (United States)

    Liu, Zhu; Gong, Zhou; Dong, Xu; Tang, Chun

    2016-01-01

    Proteins interact with each other to establish their identities in cell. The affinities for the interactions span more than ten orders of magnitude, and KD values in μM-mM regimen are considered transient and are important in cell signaling. Solution NMR including diamagnetic and paramagnetic techniques has enabled atomic-resolution depictions of transient protein-protein interactions. Diamagnetic NMR allows characterization of protein complexes with KD values up to several mM, whereas ultraweak and fleeting complexes can be modeled with the use of paramagnetic NMR especially paramagnetic relaxation enhancement (PRE). When tackling ever-larger protein complexes, PRE can be particularly useful in providing long-range intermolecular distance restraints. As NMR measurements are averaged over the ensemble of complex structures, structural information for dynamic protein-protein interactions besides the stereospecific one can often be extracted. Herein the protein interaction dynamics are exemplified by encounter complexes, alternative binding modes, and coupled binding/folding of intrinsically disordered proteins. Further integration of NMR with other biophysical techniques should allow better visualization of transient protein-protein interactions. In particular, single-molecule data may facilitate the interpretation of ensemble-averaged NMR data. Though same structures of proteins and protein complexes were found in cell as in diluted solution, we anticipate that the dynamics of transient protein protein-protein interactions be different, which awaits awaits exploration by NMR. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. PMID:25896389

  5. Protein (Viridiplantae): 308810769 [

    Lifescience Database Archive (English)

    Full Text Available XP_003082693.1 33090:1723 3041:2182 1035538:123 13792:123 70447:3706 70448:4753 K+-channel ERG a ... nd related proteins, contain PAS /PAC sensor domain (ISS) Ostreococcus tauri MHFNADL ...

  6. Protein (Viridiplantae): 308809165 [

    Lifescience Database Archive (English)

    Full Text Available XP_003081892.1 33090:2400 3041:801 1035538:331 13792:331 70447:681 70448:136 K+-channel ERG and ... related proteins, contain PAS /PAC sensor domain (ISS) Ostreococcus tauri MPSTAGM ...

  7. Protein (Viridiplantae): 357507515 [

    Lifescience Database Archive (English)

    Full Text Available XP_003624046.1 33090:6310 35493:7221 131221:7221 3193:7221 58023:3109 78536:1898 58024:1898 3398 ... 803:6139 3814:6139 163742:7708 3877:7708 3880:7708 Nematode ... resistance-like protein Medicago truncatula MTLPLA ...

  8. Protein (Viridiplantae): 225448363 [

    Lifescience Database Archive (English)

    Full Text Available XP_002268520.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... 667:4453 3602:4453 3603:4453 29760:4453 PREDICTED: nematode ... resistance protein-like HSPRO2 isoform 1 Vitis vin ...

  9. Protein (Viridiplantae): 226529483 [

    Lifescience Database Archive (English)

    Full Text Available NP_001151109.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... 0:6136 147369:6136 147429:6136 4575:6020 4577:6020 nematode -resistance protein Zea mays MATPDLSPVSPVRRDDKQCAPS ...

  10. Protein (Viridiplantae): 357125930 [

    Lifescience Database Archive (English)

    Full Text Available XP_003564642.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... :4262 147385:4262 15367:4262 15368:4262 PREDICTED: nematode ... resistance protein-like HSPRO1-like Brachypodium d ...

  11. Protein (Viridiplantae): 356553794 [

    Lifescience Database Archive (English)

    Full Text Available XP_003545237.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... 14:9870 163735:3769 3846:3769 3847:3769 PREDICTED: nematode ... resistance protein-like HSPRO2-like Glycine max MV ...

  12. Protein (Viridiplantae): 357492609 [

    Lifescience Database Archive (English)

    Full Text Available XP_003616593.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... :9870 3814:9870 163742:15503 3877:15503 3880:15503 Nematode ... resistance HS1pro1 protein Medicago truncatula MVD ...

  13. Protein (Viridiplantae): 351726303 [

    Lifescience Database Archive (English)

    Full Text Available NP_001236610.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... 803:9870 3814:9870 163735:3769 3846:3769 3847:3769 nematode ... resistance HS1pro1 protein Glycine max MVDLDWQTKMV ...

  14. Protein (Viridiplantae): 350537949 [

    Lifescience Database Archive (English)

    Full Text Available NP_001234063.1 33090:6270 35493:2337 131221:2337 3193:2337 58023:2583 78536:1868 58024:1868 3398 ... 4 424574:154 4107:154 49274:154 4081:154 root-knot nematode ... resistance protein Solanum lycopersicum MEKRKDIEEA ...

  15. Protein (Viridiplantae): 356568543 [

    Lifescience Database Archive (English)

    Full Text Available XP_003552470.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... 14:9870 163735:3769 3846:3769 3847:3769 PREDICTED: nematode ... resistance protein-like HSPRO2-like Glycine max MV ...

  16. Protein (Viridiplantae): 356560204 [

    Lifescience Database Archive (English)

    Full Text Available XP_003548384.1 33090:30695 35493:21281 131221:21281 3193:21281 58023:14619 78536:14658 58024:146 ... 14:9870 163735:3769 3846:3769 3847:3769 PREDICTED: nematode ... resistance protein-like HSPRO2-like, partial Glyci ...

  17. Combinable protein crop production

    OpenAIRE

    Wright, Isobel

    2008-01-01

    This research topic review aims to summarise research knowledge and observational experience of combinable protein crop production in organic farming systems for the UK. European research on peas, faba beans and lupins is included; considering their role in the rotation, nitrogen fixation, varieties, establishment, weed control, yields, problems experienced and intercropping with cereals.

  18. Protein (Viridiplantae): 226531780 [

    Lifescience Database Archive (English)

    Full Text Available NP_001147196.1 33090:20715 35493:21884 131221:21884 3193:21884 58023:14330 78536:14347 58024:143 ... 470 4575:5441 4577:5441 deleted in split hand/splt foot ... protein 1 Zea mays MAAAPADAKAEAAKMDLLEDDDEFEEFEIDQ ...

  19. Protein (Viridiplantae): 159468784 [

    Lifescience Database Archive (English)

    Full Text Available XP_001692554.1 33090:22049 3041:6770 3166:4229 3042:4229 3051:3540 3052:3540 3055:3540 coenzyme ... ing protein, partial Chlamydomonas reinhardtii WTPEQ LYAVVSRVEDYHLFVPWCQ KSRPAAREAGDYMEAELEVGFQ LLVERYTSQ I ... YLTPGRAVRSAVPDSSLFDHLDSTWTMEPGPAPATCWLSFHVDFAFRSQ LHGYLADLFFSEVVKQ MSNAFEGRCARLYGPSS ...

  20. Protein (Viridiplantae): 18395564 [

    Lifescience Database Archive (English)

    Full Text Available NP_027545.1 33090:256 35493:21220 131221:21220 3193:21220 58023:13487 78536:13436 58024:13436 33 ... 0:5421 980083:5421 3701:5421 3702:5521 SPFH/Band 7/PHB ... domain-containing membrane-associated protein Arab ...

  1. Protein (Viridiplantae): 15239547 [

    Lifescience Database Archive (English)

    Full Text Available NP_200221.1 33090:255 35493:10960 131221:10960 3193:10960 58023:6871 78536:476 58024:476 3398:47 ... 0:2583 980083:2583 3701:2583 3702:1873 SPFH/Band 7/PHB ... domain-containing membrane-associated protein Arab ...

  2. Protein (Viridiplantae): 18417021 [

    Lifescience Database Archive (English)

    Full Text Available NP_567778.1 33090:255 35493:10960 131221:10960 3193:10960 58023:6871 78536:476 58024:476 3398:47 ... 0:2583 980083:2583 3701:2583 3702:1873 SPFH/Band 7/PHB ... domain-containing membrane-associated protein Arab ...

  3. Protein (Viridiplantae): 42571103 [

    Lifescience Database Archive (English)

    Full Text Available NP_973625.1 33090:14975 35493:14487 131221:14487 3193:14487 58023:10069 78536:8383 58024:8383 33 ... 980083:5566 3701:5566 3702:5685 protein sodium-and lithium -tolerant 1 Arabidopsis thaliana MENMYMWVFKERPENALG ...

  4. Protein (Viridiplantae): 18404463 [

    Lifescience Database Archive (English)

    Full Text Available NP_565864.1 33090:14975 35493:14487 131221:14487 3193:14487 58023:10069 78536:8383 58024:8383 33 ... 980083:5566 3701:5566 3702:5685 protein sodium-and lithium -tolerant 1 Arabidopsis thaliana MENHHPSTLLSMDSSASS ...

  5. Protein (Viridiplantae): 255590528 [

    Lifescience Database Archive (English)

    Full Text Available XP_002535292.1 33090:897 35493:1400 131221:1400 3193:1400 58023:1784 78536:1198 58024:1198 3398: ... 5629:537 235880:537 3987:537 3988:537 Protein BABY BOOM , putative Ricinus communis MKHMTRQEFVASIRRKSSGFSRG ...

  6. Protein (Viridiplantae): 226500350 [

    Lifescience Database Archive (English)

    Full Text Available NP_001147535.1 33090:897 35493:1400 131221:1400 3193:1400 58023:1784 78536:1198 58024:1198 3398: ... 7369:454 147429:454 4575:168 4577:168 protein BABY BOOM ... 1 Zea mays MASANNWLGFSLSGQDNPQPNQDSSPAAGIDISGASDFY ...

  7. Protein (Viridiplantae): 255585676 [

    Lifescience Database Archive (English)

    Full Text Available XP_002533523.1 33090:897 35493:1400 131221:1400 3193:1400 58023:1784 78536:1198 58024:1198 3398: ... 5629:537 235880:537 3987:537 3988:537 Protein BABY BOOM , putative Ricinus communis MAPATTNWLSFSLSPMEMLRSST ...

  8. Protein (Viridiplantae): 308807062 [

    Lifescience Database Archive (English)

    Full Text Available XP_003080842.1 33090:2448 3041:440 1035538:347 13792:347 70447:323 70448:86 FTSH1_SYNY3 Cell ... div ... ision protein ftsH homolog 1 dbj|BAA10230.1| cell ... division prot (ISS) Ostreococcus tauri MRAHFRASVRA ...

  9. Protein Thin Film Machines

    OpenAIRE

    Federici, Stefania; Oliviero, Giulio; Hamad-Schifferli, Kimberly; Bergese, Paolo

    2010-01-01

    We report the first example of microcantilever beams that are reversibly driven by protein thin film machines fuelled by cycling the salt concentration of the surrounding solution. We also show that upon the same salinity stimulus the drive can be completely reversed in its direction by introducing a surface coating ligand. Experimental results are throughout discussed within a general yet simple thermodynamic model.

  10. Protein (Viridiplantae): 255541926 [

    Lifescience Database Archive (English)

    Full Text Available XP_002512027.1 33090:26381 35493:16326 131221:16326 3193:16326 58023:13222 78536:13135 58024:131 ... 7:4031 235629:4031 235880:4031 3987:4031 3988:4031 Ethanol ... tolerance protein GEKO1, putative Ricinus communis ...

  11. Protein (Viridiplantae): 30693285 [

    Lifescience Database Archive (English)

    Full Text Available NP_198682.3 33090:122 35493:14455 131221:14455 3193:14455 58023:10070 78536:8442 58024:8442 3398 ... 83:3647 3701:3647 3702:3409 protein acclimation of photosynthesis ... to environment Arabidopsis thaliana MGSITVAPGTTVLF ...

  12. Protein (Viridiplantae): 334188069 [

    Lifescience Database Archive (English)

    Full Text Available NP_001190435.1 33090:122 35493:14455 131221:14455 3193:14455 58023:10070 78536:8442 58024:8442 3 ... 83:3647 3701:3647 3702:3409 protein acclimation of photosynthesis ... to environment Arabidopsis thaliana MGSITVAPGTTVLF ...

  13. Protein (Viridiplantae): 15233302 [

    Lifescience Database Archive (English)

    Full Text Available NP_191115.1 33090:10299 35493:193 131221:193 3193:193 58023:114 78536:2677 58024:2677 3398:2677 ... 083:3094 3701:3094 3702:2636 AT-hook protein of GA feedback ... 2 Arabidopsis thaliana MANPWWVGNVAIGGVESPVTSSAPSLH ...

  14. Protein (Viridiplantae): 30690333 [

    Lifescience Database Archive (English)

    Full Text Available NP_195265.2 33090:10299 35493:193 131221:193 3193:193 58023:114 78536:2677 58024:2677 3398:2677 ... 083:3094 3701:3094 3702:2636 AT-hook protein of GA feedback ... 1 Arabidopsis thaliana MSSYMHPLLGQELHLQRPEDSRTPPDQ ...

  15. Protein (Viridiplantae): 357439925 [

    Lifescience Database Archive (English)

    Full Text Available XP_003590240.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... 249 3803:249 3814:249 163742:554 3877:554 3880:554 CRM ... domain-containing protein, putative Medicago trunc ...

  16. Protein (Viridiplantae): 15232195 [

    Lifescience Database Archive (English)

    Full Text Available NP_189392.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 71 ... :2768 3701:2768 3702:2151 RNA-binding CRS1 / YhbY (CRM ) domain protein Arabidopsis thaliana MNQVFKGWSRGMS ...

  17. Protein (Viridiplantae): 357439975 [

    Lifescience Database Archive (English)

    Full Text Available XP_003590265.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... 249 3803:249 3814:249 163742:554 3877:554 3880:554 CRM ... domain-containing protein, putative Medicago trunc ...

  18. Protein (Viridiplantae): 15226402 [

    Lifescience Database Archive (English)

    Full Text Available NP_180415.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 71 ... :2768 3701:2768 3702:2151 RNA-binding CRS1 / YhbY (CRM ) domain protein Arabidopsis thaliana MAIAFARGLRKAS ...

  19. Protein (Viridiplantae): 225448146 [

    Lifescience Database Archive (English)

    Full Text Available XP_002263852.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... :525 3603:525 29760:525 PREDICTED: uncharacterized CRM ... domain-containing protein At3g25440, chloroplastic ...

  20. Protein (Viridiplantae): 79417439 [

    Lifescience Database Archive (English)

    Full Text Available NP_189171.2 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 71 ... 68 980083:2768 3701:2768 3702:2151 uncharacterized CRM ... domain-containing protein Arabidopsis thaliana MGF ...

  1. Protein (Viridiplantae): 145332683 [

    Lifescience Database Archive (English)

    Full Text Available NP_001078207.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... 68 980083:2768 3701:2768 3702:2151 uncharacterized CRM ... domain-containing protein Arabidopsis thaliana MWN ...

  2. Protein (Viridiplantae): 240254502 [

    Lifescience Database Archive (English)

    Full Text Available NP_179731.4 33090:11082 35493:11019 131221:11019 3193:11019 58023:8723 78536:6595 58024:6595 339 ... :4699 3701:4699 3702:4683 RNA-binding CRS1 / YhbY (CRM ) domain protein Arabidopsis thaliana MATAKSSTLTNLI ...

  3. Protein (Viridiplantae): 42566743 [

    Lifescience Database Archive (English)

    Full Text Available NP_193043.2 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 71 ... :2768 3701:2768 3702:2151 RNA-binding CRS1 / YhbY (CRM ) domain protein Arabidopsis thaliana MLALGYAKEIAQR ...

  4. Protein (Viridiplantae): 15229636 [

    Lifescience Database Archive (English)

    Full Text Available NP_188468.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 71 ... :2768 980083:2768 3701:2768 3702:2151 CRS1 / YhbY (CRM ) domain-containing protein Arabidopsis thaliana MA ...

  5. Protein (Viridiplantae): 225444203 [

    Lifescience Database Archive (English)

    Full Text Available XP_002270373.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... :525 3603:525 29760:525 PREDICTED: uncharacterized CRM ... domain-containing protein At3g25440, chloroplastic ...

  6. Protein (Viridiplantae): 357478871 [

    Lifescience Database Archive (English)

    Full Text Available XP_003609721.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... 249 3803:249 3814:249 163742:554 3877:554 3880:554 CRM ... domain-containing protein, putative Medicago trunc ...

  7. Protein (Viridiplantae): 334187011 [

    Lifescience Database Archive (English)

    Full Text Available NP_194704.2 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 71 ... :2768 980083:2768 3701:2768 3702:2151 CRS1 / YhbY (CRM ) domain-containing protein Arabidopsis thaliana MA ...

  8. Protein (Viridiplantae): 357167884 [

    Lifescience Database Archive (English)

    Full Text Available XP_003581379.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... 6 15367:4086 15368:4086 PREDICTED: uncharacterized CRM ... domain-containing protein At3g25440, chloroplastic ...

  9. Protein (Viridiplantae): 357521229 [

    Lifescience Database Archive (English)

    Full Text Available XP_003630903.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... 249 3803:249 3814:249 163742:554 3877:554 3880:554 CRM ... domain-containing protein, putative Medicago trunc ...

  10. Protein (Viridiplantae): 357124470 [

    Lifescience Database Archive (English)

    Full Text Available XP_003563923.1 33090:207 35493:345 131221:345 3193:345 58023:188 78536:6156 58024:6156 3398:6156 ... 6 15367:4086 15368:4086 PREDICTED: uncharacterized CRM ... domain-containing protein At3g25440, chloroplastic ...

  11. Protein (Viridiplantae): 357467665 [

    Lifescience Database Archive (English)

    Full Text Available XP_003604117.1 33090:7684 35493:9413 131221:9413 3193:9413 58023:4125 78536:6265 58024:6265 3398 ... :7265 3814:7265 163742:15887 3877:15887 3880:15887 StAR -related lipid transfer protein Medicago truncatula ...

  12. Protein (Viridiplantae): 15236909 [

    Lifescience Database Archive (English)

    Full Text Available NP_194422.1 33090:7490 35493:1858 131221:1858 3193:1858 58023:4234 78536:3190 58024:3190 3398:31 ... 22 3699:122 3700:122 980083:122 3701:122 3702:1780 StAR -related lipid-transfer protein Arabidopsis thalian ...

  13. Protein (Viridiplantae): 357464181 [

    Lifescience Database Archive (English)

    Full Text Available XP_003602372.1 33090:7684 35493:9413 131221:9413 3193:9413 58023:4125 78536:6265 58024:6265 3398 ... :7265 3814:7265 163742:15887 3877:15887 3880:15887 StAR -related lipid transfer protein Medicago truncatula ...

  14. Protein (Viridiplantae): 357464183 [

    Lifescience Database Archive (English)

    Full Text Available XP_003602373.1 33090:7684 35493:9413 131221:9413 3193:9413 58023:4125 78536:6265 58024:6265 3398 ... :7265 3814:7265 163742:15887 3877:15887 3880:15887 StAR -related lipid transfer protein Medicago truncatula ...

  15. Protein (Viridiplantae): 357467663 [

    Lifescience Database Archive (English)

    Full Text Available XP_003604116.1 33090:7684 35493:9413 131221:9413 3193:9413 58023:4125 78536:6265 58024:6265 3398 ... :7265 3814:7265 163742:15887 3877:15887 3880:15887 StAR -related lipid transfer protein Medicago truncatula ...

  16. Protein (Viridiplantae): 255568289 [

    Lifescience Database Archive (English)

    Full Text Available XP_002525119.1 33090:1951 35493:1293 131221:1293 3193:1293 58023:2877 78536:1422 58024:1422 3398 ... 977:13 235629:13 235880:13 3987:13 3988:13 Adaptin ear -binding coat-associated protein, putative Ricinus ...

  17. Protein (Viridiplantae): 18410992 [

    Lifescience Database Archive (English)

    Full Text Available NP_567071.1 33090:1951 35493:1293 131221:1293 3193:1293 58023:2877 78536:1422 58024:1422 3398:14 ... 239 3700:239 980083:239 3701:239 3702:5411 Adaptin ear -binding coat-associated protein 1 NECAP-1 Arabidop ...

  18. Protein (Viridiplantae): 255577954 [

    Lifescience Database Archive (English)

    Full Text Available XP_002529849.1 33090:1951 35493:1293 131221:1293 3193:1293 58023:2877 78536:1422 58024:1422 3398 ... 977:13 235629:13 235880:13 3987:13 3988:13 Adaptin ear -binding coat-associated protein, putative Ricinus ...

  19. Protein (Viridiplantae): 226509020 [

    Lifescience Database Archive (English)

    Full Text Available NP_001152713.1 33090:451 35493:523 131221:523 3193:523 58023:837 78536:8759 58024:8759 3398:8759 ... 147369:5146 147429:5146 4575:1047 4577:1047 MFT2 - Corn ... MFT-like protein Zea mays MARFVDPLVVGRVIGEVVDLFVPS ...

  20. Protein (Viridiplantae): 226532395 [

    Lifescience Database Archive (English)

    Full Text Available NP_001147266.1 33090:451 35493:523 131221:523 3193:523 58023:837 78536:8759 58024:8759 3398:8759 ... 147369:5146 147429:5146 4575:1047 4577:1047 MFT2 - Corn ... MFT-like protein Zea mays MARFVDPLVVGRVIGEVVDLFVPS ...

  1. Protein (Cyanobacteria): 28418 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18827726.1 1117:517 1118:7626 1125:2051 1126:2469 1160281:2759 Type 4 prepilin-like proteins ... leader ... peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  2. Protein (Cyanobacteria): 28422 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18817031.1 1117:517 1118:7626 1125:2051 1126:2469 1160280:2213 Type 4 prepilin-like proteins ... leader ... peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  3. Protein (Cyanobacteria): 28419 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18835633.1 1117:517 1118:7626 1125:2051 1126:2469 1160283:2051 Type 4 prepilin-like proteins ... leader ... peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  4. Protein (Cyanobacteria): 28417 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18822668.1 1117:517 1118:7626 1125:2051 1126:2469 1160286:2656 Type 4 prepilin-like proteins ... leader ... peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  5. Protein (Cyanobacteria): 28421 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18849476.1 1117:517 1118:7626 1125:2051 1126:2469 721123:1760 Type 4 prepilin-like proteins leader ... eader peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  6. Protein (Cyanobacteria): 28415 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18831825.1 1117:517 1118:7626 1125:2051 1126:2469 213618:2396 Type 4 prepilin-like proteins leader ... eader peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  7. Protein (Cyanobacteria): 28416 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18841888.1 1117:517 1118:7626 1125:2051 1126:2469 1160284:2857 Type 4 prepilin-like proteins ... leader ... peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  8. Protein (Cyanobacteria): 28420 [

    Lifescience Database Archive (English)

    Full Text Available ZP_18844408.1 1117:517 1118:7626 1125:2051 1126:2469 1160285:1581 Type 4 prepilin-like proteins ... leader ... peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  9. Protein (Cyanobacteria): 28414 [

    Lifescience Database Archive (English)

    Full Text Available ZP_16388674.1 1117:517 1118:7626 1125:2051 1126:2469 1160282:309 Type 4 prepilin-like proteins leader ... eader peptide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis aerug ...

  10. Protein (Viridiplantae): 359494868 [

    Lifescience Database Archive (English)

    Full Text Available XP_003634859.1 33090:7785 35493:2083 131221:2083 3193:2083 58023:1440 78536:1643 58024:1643 3398 ... 403667:299 3602:299 3603:299 29760:299 PREDICTED: influenza ... virus NS1A-binding protein homolog Vitis vinifera ...

  11. Protein (Viridiplantae): 359496826 [

    Lifescience Database Archive (English)

    Full Text Available XP_003635348.1 33090:7785 35493:2083 131221:2083 3193:2083 58023:1440 78536:1643 58024:1643 3398 ... 403667:299 3602:299 3603:299 29760:299 PREDICTED: influenza ... virus NS1A-binding protein homolog Vitis vinifera ...

  12. Protein (Viridiplantae): 255547720 [

    Lifescience Database Archive (English)

    Full Text Available XP_002514917.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7 ... 235629:4243 235880:4243 3987:4243 3988:4243 Small rubber ... particle protein, putative Ricinus communis METEKK ...

  13. Protein (Viridiplantae): 30697500 [

    Lifescience Database Archive (English)

    Full Text Available NP_849856.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7124 ... 699:3534 3700:3534 980083:3534 3701:3534 3702:3251 Rubber ... elongation factor protein (REF) Arabidopsis thalia ...

  14. Protein (Viridiplantae): 15230002 [

    Lifescience Database Archive (English)

    Full Text Available NP_187201.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7124 ... 699:3534 3700:3534 980083:3534 3701:3534 3702:3251 Rubber ... elongation factor protein Arabidopsis thaliana MAT ...

  15. Protein (Viridiplantae): 15220426 [

    Lifescience Database Archive (English)

    Full Text Available NP_176904.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7124 ... 699:3534 3700:3534 980083:3534 3701:3534 3702:3251 Rubber ... elongation factor protein (REF) Arabidopsis thalia ...

  16. Protein (Viridiplantae): 255542728 [

    Lifescience Database Archive (English)

    Full Text Available XP_002512427.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7 ... 7:4243 235629:4243 235880:4243 3987:4243 3988:4243 Rubber ... elongation factor protein, putative Ricinus commun ...

  17. Protein (Viridiplantae): 297841421 [

    Lifescience Database Archive (English)

    Full Text Available XP_002888592.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7 ... 0:3534 980083:3534 3701:3534 59689:7990 81972:7990 rubber ... elongation factor family protein Arabidopsis lyrat ...

  18. Protein (Viridiplantae): 255582180 [

    Lifescience Database Archive (English)

    Full Text Available XP_002531884.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7 ... 235629:4243 235880:4243 3987:4243 3988:4243 Small rubber ... particle protein, putative Ricinus communis MAESEV ...

  19. Protein (Viridiplantae): 297829074 [

    Lifescience Database Archive (English)

    Full Text Available XP_002882419.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7 ... 0:3534 980083:3534 3701:3534 59689:7990 81972:7990 rubber ... elongation factor family protein Arabidopsis lyrat ...

  20. Protein (Viridiplantae): 15227131 [

    Lifescience Database Archive (English)

    Full Text Available NP_182299.1 33090:975 35493:959 131221:959 3193:959 58023:1582 78536:423 58024:423 3398:423 7124 ... 699:3534 3700:3534 980083:3534 3701:3534 3702:3251 Rubber ... elongation factor protein (REF) Arabidopsis thalia ...

  1. Protein (Viridiplantae): 15219200 [

    Lifescience Database Archive (English)

    Full Text Available NP_178006.1 33090:6322 35493:2262 131221:2262 3193:2262 58023:2407 78536:1099 58024:1099 3398:10 ... 514 3702:695 D-mannose binding lectin protein with Apple -like carbohydrate-binding domain Arabidopsis thali ...

  2. Protein (Viridiplantae): 15230565 [

    Lifescience Database Archive (English)

    Full Text Available NP_190739.1 33090:6322 35493:2262 131221:2262 3193:2262 58023:2407 78536:1099 58024:1099 3398:10 ... 514 3702:895 D-mannose binding lectin protein with Apple -like carbohydrate-binding domain Arabidopsis thali ...

  3. Protein (Viridiplantae): 15219197 [

    Lifescience Database Archive (English)

    Full Text Available NP_178003.1 33090:6322 35493:2262 131221:2262 3193:2262 58023:2407 78536:1099 58024:1099 3398:10 ... 514 3702:695 D-mannose binding lectin protein with Apple -like carbohydrate-binding domain Arabidopsis thali ...

  4. Protein Requirements during Aging.

    Science.gov (United States)

    Courtney-Martin, Glenda; Ball, Ronald O; Pencharz, Paul B; Elango, Rajavel

    2016-01-01

    Protein recommendations for elderly, both men and women, are based on nitrogen balance studies. They are set at 0.66 and 0.8 g/kg/day as the estimated average requirement (EAR) and recommended dietary allowance (RDA), respectively, similar to young adults. This recommendation is based on single linear regression of available nitrogen balance data obtained at test protein intakes close to or below zero balance. Using the indicator amino acid oxidation (IAAO) method, we estimated the protein requirement in young adults and in both elderly men and women to be 0.9 and 1.2 g/kg/day as the EAR and RDA, respectively. This suggests that there is no difference in requirement on a gender basis or on a per kg body weight basis between younger and older adults. The requirement estimates however are ~40% higher than the current protein recommendations on a body weight basis. They are also 40% higher than our estimates in young men when calculated on the basis of fat free mass. Thus, current recommendations may need to be re-assessed. Potential rationale for this difference includes a decreased sensitivity to dietary amino acids and increased insulin resistance in the elderly compared with younger individuals. PMID:27529275

  5. Protein Requirements during Aging

    Directory of Open Access Journals (Sweden)

    Glenda Courtney-Martin

    2016-08-01

    Full Text Available Protein recommendations for elderly, both men and women, are based on nitrogen balance studies. They are set at 0.66 and 0.8 g/kg/day as the estimated average requirement (EAR and recommended dietary allowance (RDA, respectively, similar to young adults. This recommendation is based on single linear regression of available nitrogen balance data obtained at test protein intakes close to or below zero balance. Using the indicator amino acid oxidation (IAAO method, we estimated the protein requirement in young adults and in both elderly men and women to be 0.9 and 1.2 g/kg/day as the EAR and RDA, respectively. This suggests that there is no difference in requirement on a gender basis or on a per kg body weight basis between younger and older adults. The requirement estimates however are ~40% higher than the current protein recommendations on a body weight basis. They are also 40% higher than our estimates in young men when calculated on the basis of fat free mass. Thus, current recommendations may need to be re-assessed. Potential rationale for this difference includes a decreased sensitivity to dietary amino acids and increased insulin resistance in the elderly compared with younger individuals.

  6. Protein (Viridiplantae): 357437225 [

    Lifescience Database Archive (English)

    Full Text Available XP_003588888.1 33090:11850 35493:11195 131221:11195 3193:11195 58023:7061 78536:6038 58024:6038 ... 5 91835:7640 72025:8712 3803:8712 3814:8712 163742:12345 ... 3877:12345 ... 3880:12345 ... hypothetical protein MTR_1g0 ...

  7. Protein (Viridiplantae): 168024037 [

    Lifescience Database Archive (English)

    Full Text Available XP_001764543.1 33090:26221 35493:16132 131221:16132 3193:16132 3208:12345 ... 404260:12345 ... 3214:12345 ... 5 114656:12345 ... 3215:12345 ... 3216:12345 ... 3217:12345 ... 3218:12345 ... 145481 ... :12345 ... predicted protein Physcomitrella patens subsp. pat ...

  8. Protein (Viridiplantae): 255588560 [

    Lifescience Database Archive (English)

    Full Text Available XP_002534643.1 33090:54663 35493:45756 131221:45756 3193:45756 58023:34361 78536:34515 58024:345 ... 62 235629:11062 235880:11062 3987:11062 3988:11062 Biopolymer ... transport exbD1 protein, putative Ricinus communis ...

  9. Protein (Viridiplantae): 255588558 [

    Lifescience Database Archive (English)

    Full Text Available XP_002534642.1 33090:54662 35493:45755 131221:45755 3193:45755 58023:34360 78536:34514 58024:345 ... 61 235629:11061 235880:11061 3987:11061 3988:11061 Biopolymer ... transport exbB protein, putative Ricinus communis ...

  10. Protein (Viridiplantae): 255593120 [

    Lifescience Database Archive (English)

    Full Text Available XP_002535793.1 33090:54662 35493:45755 131221:45755 3193:45755 58023:34360 78536:34514 58024:345 ... 61 235629:11061 235880:11061 3987:11061 3988:11061 Biopolymer ... transport exbB protein, putative Ricinus communis ...

  11. Protein (Viridiplantae): 357453997 [

    Lifescience Database Archive (English)

    Full Text Available XP_003597279.1 33090:16324 35493:17354 131221:17354 3193:17354 58023:13519 78536:13471 58024:134 ... 2531 3814:12531 163742:14737 3877:14737 3880:14737 Cat ... eye syndrome critical region protein Medicago trun ...

  12. Protein (Viridiplantae): 226501984 [

    Lifescience Database Archive (English)

    Full Text Available NP_001152161.1 33090:16324 35493:17354 131221:17354 3193:17354 58023:13519 78536:13471 58024:134 ... 0:3521 147369:3521 147429:3521 4575:4966 4577:4966 cat ... eye syndrome critical region protein 5 Zea mays MR ...

  13. Protein (Viridiplantae): 15234540 [

    Lifescience Database Archive (English)

    Full Text Available NP_193892.1 33090:988 35493:13743 131221:13743 3193:13743 58023:94 78536:8446 58024:8446 3398:84 ... 699:2376 3700:2376 980083:2376 3701:2376 3702:1438 lsd ... one like 2 protein Arabidopsis thaliana MEEIQQQTQK ...

  14. Protein (Viridiplantae): 18398482 [

    Lifescience Database Archive (English)

    Full Text Available NP_564405.1 33090:988 35493:13743 131221:13743 3193:13743 58023:94 78536:8446 58024:8446 3398:84 ... 699:2376 3700:2376 980083:2376 3701:2376 3702:1438 lsd ... one like 1 protein Arabidopsis thaliana MPVPLAPYPT ...

  15. Protein (Viridiplantae): 42570227 [

    Lifescience Database Archive (English)

    Full Text Available NP_849742.2 33090:988 35493:13743 131221:13743 3193:13743 58023:94 78536:8446 58024:8446 3398:84 ... 699:2376 3700:2376 980083:2376 3701:2376 3702:1438 lsd ... one like 1 protein Arabidopsis thaliana MHTWKNQIFS ...

  16. Protein (Viridiplantae): 186479127 [

    Lifescience Database Archive (English)

    Full Text Available NP_001117399.1 33090:988 35493:13743 131221:13743 3193:13743 58023:94 78536:8446 58024:8446 3398 ... 699:2376 3700:2376 980083:2376 3701:2376 3702:1438 lsd ... one like 1 protein Arabidopsis thaliana MPVPLAPYPT ...

  17. Thermal unfolding of proteins

    OpenAIRE

    Cieplak, Marek; Sulkowska, Joanna I.

    2006-01-01

    Thermal unfolding of proteins is compared to folding and mechanical stretching in a simple topology-based dynamical model. We define the unfolding time and demonstrate its low-temperature divergence. Below a characteristic temperature, contacts break at separate time scales and unfolding proceeds approximately in a way reverse to folding. Features in these scenarios agree with experiments and atomic simulations on titin.

  18. Thermal unfolding of proteins

    Science.gov (United States)

    Cieplak, Marek; Sułkowska, Joanna I.

    2005-11-01

    Thermal unfolding of proteins is compared to folding and mechanical stretching in a simple topology-based dynamical model. We define the unfolding time and demonstrate its low-temperature divergence. Below a characteristic temperature, contacts break at separate time scales and unfolding proceeds approximately in a way reverse to folding. Features in these scenarios agree with experiments and atomic simulations on titin.

  19. Protein (Viridiplantae): 30698814 [

    Lifescience Database Archive (English)

    Full Text Available NP_177324.2 33090:6429 35493:2153 131221:2153 3193:2153 58023:2922 78536:756 58024:756 3398:756 ... 01:7638 3702:7984 capping protein (actin filament) muscle ... Z-line, beta Arabidopsis thaliana MEAALGLLRRMPPKQS ...

  20. Protein (Viridiplantae): 240254201 [

    Lifescience Database Archive (English)

    Full Text Available NP_174750.4 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:7947 7 ... 0083:7173 3701:7173 3702:7453 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  1. Protein (Viridiplantae): 18413327 [

    Lifescience Database Archive (English)

    Full Text Available NP_567355.1 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:7947 7 ... 0083:5499 3701:5499 3702:5612 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  2. Protein (Viridiplantae): 18397885 [

    Lifescience Database Archive (English)

    Full Text Available NP_564377.1 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:7947 7 ... 0083:5499 3701:5499 3702:5612 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  3. Protein (Viridiplantae): 22330031 [

    Lifescience Database Archive (English)

    Full Text Available NP_175121.2 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:7947 7 ... 0083:7173 3701:7173 3702:7453 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  4. Protein (Viridiplantae): 30693154 [

    Lifescience Database Archive (English)

    Full Text Available NP_174751.2 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:7947 7 ... 0083:7173 3701:7173 3702:7453 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  5. Protein (Viridiplantae): 15230950 [

    Lifescience Database Archive (English)

    Full Text Available NP_189224.1 33090:1851 35493:568 131221:568 3193:568 58023:378 78536:1039 58024:1039 3398:1039 7 ... 980083:388 3701:388 3702:2630 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  6. Protein (Viridiplantae): 18395035 [

    Lifescience Database Archive (English)

    Full Text Available NP_564152.1 33090:10991 35493:11467 131221:11467 3193:11467 58023:7243 78536:6148 58024:6148 339 ... 4 980083:14 3701:14 3702:5507 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  7. Protein (Viridiplantae): 357463503 [

    Lifescience Database Archive (English)

    Full Text Available XP_003602033.1 33090:10991 35493:11467 131221:11467 3193:11467 58023:7243 78536:6148 58024:6148 ... 1543 3814:11543 163742:15806 3877:15806 3880:15806 TLC ... domain-containing protein Medicago truncatula MAKK ...

  8. Protein (Viridiplantae): 22328807 [

    Lifescience Database Archive (English)

    Full Text Available NP_680724.1 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:7947 7 ... 0083:5499 3701:5499 3702:5612 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  9. Protein (Viridiplantae): 238478639 [

    Lifescience Database Archive (English)

    Full Text Available NP_001154368.1 33090:9039 35493:11752 131221:11752 3193:11752 58023:7721 78536:6590 58024:6590 3 ... 0083:3773 3701:3773 3702:4297 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  10. Protein (Viridiplantae): 356518541 [

    Lifescience Database Archive (English)

    Full Text Available XP_003527937.1 33090:10991 35493:11467 131221:11467 3193:11467 58023:7243 78536:6148 58024:6148 ... 4:11543 163735:6135 3846:6135 3847:6135 PREDICTED: TLC ... domain-containing protein 2-like Glycine max MGGGK ...

  11. Protein (Viridiplantae): 79319015 [

    Lifescience Database Archive (English)

    Full Text Available NP_001031121.1 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:794 ... 0083:5499 3701:5499 3702:5612 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  12. Protein (Viridiplantae): 79325051 [

    Lifescience Database Archive (English)

    Full Text Available NP_001031610.1 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:794 ... 0083:5499 3701:5499 3702:5612 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  13. Protein (Viridiplantae): 15232128 [

    Lifescience Database Archive (English)

    Full Text Available NP_189363.1 33090:1851 35493:568 131221:568 3193:568 58023:378 78536:1039 58024:1039 3398:1039 7 ... 980083:388 3701:388 3702:2630 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  14. Protein (Viridiplantae): 30684833 [

    Lifescience Database Archive (English)

    Full Text Available NP_849545.1 33090:1851 35493:568 131221:568 3193:568 58023:377 78536:7947 58024:7947 3398:7947 7 ... 0083:5499 3701:5499 3702:5612 TRAM, LAG1 and CLN8 (TLC ) lipid-sensing domain containing protein Arabidops ...

  15. Protein oxidation and ageing

    DEFF Research Database (Denmark)

    Linton, S; Davies, Michael Jonathan; Dean, R T

    2001-01-01

    of redox-active metal ions that could catalyse oxidant formation. As a result of this decrease in antioxidant defences, and increased rate of ROS formation, it is possible that the impact of ROS increases with age. ROS are known to oxidise biological macromolecules, with proteins an important target...

  16. Mobility of photosynthetic proteins

    Czech Academy of Sciences Publication Activity Database

    Kaňa, Radek

    2013-01-01

    Roč. 116, 2-3 (2013), s. 465-479. ISSN 0166-8595 R&D Projects: GA ČR GAP501/12/0304; GA MŠk(CZ) ED2.1.00/03.0110 Institutional support: RVO:61388971 Keywords : Photosynthesis * Protein mobility * FRAP Subject RIV: EE - Microbiology, Virology Impact factor: 3.185, year: 2013

  17. Protein (Viridiplantae): 297844542 [

    Lifescience Database Archive (English)

    Full Text Available XP_002890152.1 33090:1045 35493:1883 131221:1883 3193:1883 58023:1713 78536:1480 58024:1480 3398 ... 7 3700:517 980083:517 3701:517 59689:609 81972:609 TMS ... membrane family protein Arabidopsis lyrata subsp. ...

  18. Protein (Viridiplantae): 297826769 [

    Lifescience Database Archive (English)

    Full Text Available XP_002881267.1 33090:1045 35493:1883 131221:1883 3193:1883 58023:1713 78536:1480 58024:1480 3398 ... 7 3700:517 980083:517 3701:517 59689:609 81972:609 TMS ... membrane family protein Arabidopsis lyrata subsp. ...

  19. Protein (Viridiplantae): 297829140 [

    Lifescience Database Archive (English)

    Full Text Available XP_002882452.1 33090:1045 35493:1883 131221:1883 3193:1883 58023:1713 78536:1480 58024:1480 3398 ... 7 3700:517 980083:517 3701:517 59689:609 81972:609 TMS ... membrane family protein Arabidopsis lyrata subsp. ...

  20. Protein (Viridiplantae): 297835532 [

    Lifescience Database Archive (English)

    Full Text Available XP_002885648.1 33090:1045 35493:1883 131221:1883 3193:1883 58023:1713 78536:1480 58024:1480 3398 ... 7 3700:517 980083:517 3701:517 59689:609 81972:609 TMS ... membrane family protein Arabidopsis lyrata subsp. ...

  1. Protein (Viridiplantae): 22327636 [

    Lifescience Database Archive (English)

    Full Text Available NP_199553.2 33090:1722 35493:20777 131221:20777 3193:20777 58023:13588 78536:13546 58024:13546 3 ... 83:5979 3701:5979 3702:6150 tryptophan RNA-binding attenuator -like protein Arabidopsis thaliana MAAPFFSTPFQPYVYQ ...

  2. Protein (Viridiplantae): 357116578 [

    Lifescience Database Archive (English)

    Full Text Available XP_003560057.1 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 15367:3000 15368:3000 PREDICTED: protein TIME FOR COFFEE -like Brachypodium distachyon MIGVPVPRKARSASTKRSSHE ...

  3. Protein (Viridiplantae): 356536773 [

    Lifescience Database Archive (English)

    Full Text Available XP_003536909.1 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 96 3846:5196 3847:5196 PREDICTED: protein TIME FOR COFFEE -like Glycine max MDRTRESRRSSMTTSTNGFPKRRHRTIALRDSS ...

  4. Protein (Viridiplantae): 186510319 [

    Lifescience Database Archive (English)

    Full Text Available NP_001118676.1 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 8 980083:2818 3701:2818 3702:2235 protein TIME FOR COFFEE ... Arabidopsis thaliana MDRNREARRVPMAAAGNGLSRRRHRAGSF ...

  5. Protein (Viridiplantae): 356575829 [

    Lifescience Database Archive (English)

    Full Text Available XP_003556039.1 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 96 3846:5196 3847:5196 PREDICTED: protein TIME FOR COFFEE -like Glycine max MDRIREARRSTMAANGLTRRRHRTNNSLRDSPE ...

  6. Protein (Viridiplantae): 357444275 [

    Lifescience Database Archive (English)

    Full Text Available XP_003592415.1 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 63742:12887 3877:12887 3880:12887 Protein TIME FOR COFFEE ... Medicago truncatula MDRIREARRSTMAANGLTRRRHRTNSLRDS ...

  7. Protein (Viridiplantae): 359477506 [

    Lifescience Database Archive (English)

    Full Text Available XP_002277982.2 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 1 3603:5721 29760:5721 PREDICTED: protein TIME FOR COFFEE -like Vitis vinifera MDRNREARRASMGTSNGLSRRRHRSSSLRD ...

  8. Protein (Viridiplantae): 359479681 [

    Lifescience Database Archive (English)

    Full Text Available XP_002272732.2 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 1 3603:5721 29760:5721 PREDICTED: protein TIME FOR COFFEE -like Vitis vinifera MAATNGLSRRRQRSSSLRDTPEEDGQVDLP ...

  9. Protein (Viridiplantae): 357440721 [

    Lifescience Database Archive (English)

    Full Text Available XP_003590638.1 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 ... 63742:12887 3877:12887 3880:12887 Protein TIME FOR COFFEE ... Medicago truncatula MDRIRESRKSNGFPRHRHRNLEYEAVELRE ...

  10. Protein (Viridiplantae): 18403361 [

    Lifescience Database Archive (English)

    Full Text Available NP_566705.1 33090:13671 35493:12750 131221:12750 3193:12750 58023:9989 78536:6448 58024:6448 339 ... 8 980083:2818 3701:2818 3702:2235 protein TIME FOR COFFEE ... Arabidopsis thaliana MDRNREARRVPMAAAGNGLSRRRHRAGSF ...

  11. Protein (Viridiplantae): 356564268 [

    Lifescience Database Archive (English)

    Full Text Available XP_003550377.1 33090:672 35493:1481 131221:1481 3193:1481 58023:3852 78536:2780 58024:2780 3398: ... 814:981 163735:1038 3846:1038 3847:1038 PREDICTED: random ... slug protein 5-like Glycine max MFHRWSNSHQQDQGSSEL ...

  12. Protein (Viridiplantae): 18401727 [

    Lifescience Database Archive (English)

    Full Text Available NP_029426.1 33090:21008 35493:15650 131221:15650 3193:15650 58023:14656 78536:14697 58024:14697 ... 699:5639 3700:5639 980083:5639 3701:5639 3702:5762 SAND ... family protein Arabidopsis thaliana MATSDSRSSPSSSD ...

  13. Protein (Viridiplantae): 297822433 [

    Lifescience Database Archive (English)

    Full Text Available XP_002879099.1 33090:21008 35493:15650 131221:15650 3193:15650 58023:14656 78536:14697 58024:146 ... 0:5639 980083:5639 3701:5639 59689:7788 81972:7788 sand ... family protein Arabidopsis lyrata subsp. lyrata MA ...

  14. Protein–protein interactions

    NARCIS (Netherlands)

    Janin, J.; Bonvin, A.M.J.J.

    2013-01-01

    We are proud to present the first edition of the Protein–protein interactions Section of Current Opinion in Structural Biology. The Section is new, but the topic has been present in the journal from the very start. Volume 1, Issue 1, dated February 1991, had a review by Janin entitled Protein–protei

  15. Proteins and their crystals

    Czech Academy of Sciences Publication Activity Database

    Kutá-Smatanová, Ivana; Hogg, T.; Hilgenfeld, R.; Grandori, R.; Carey, J.; Vácha, František; Štys, D.

    2003-01-01

    Roč. 10, - (2003), s. 30-31. ISSN 1211-5894 R&D Projects: GA MŠk LN00A141; GA ČR GA206/00/D007 Institutional research plan: CEZ:MSM 123100001 Keywords : antiviral proteins Subject RIV: CD - Macromolecular Chemistry

  16. Thermodynamics of meat proteins

    NARCIS (Netherlands)

    Sman, van der R.G.M.

    2012-01-01

    We describe the water activity of meat, being a mixture of proteins, salts and water, by the Free-Volume-Flory–Huggins (FVFH) theory augmented with the equation. Earlier, the FVFH theory is successfully applied to describe the thermodynamics to glucose homopolymers like starch, dextrans and maltodex

  17. Protein (Cyanobacteria): 274905 [PGDBj - Ortholog DB

    Lifescience Database Archive (English)

    Full Text Available ASVISLTPLPVVDLLATAAVNAQMVVEIGKIYGCELNMERGRELALSLGKTLASLGIVKGAIQILSTTLRLNLATYVVGKAIQGVTAAYLIRIAGKSFIEYFRNDQDWGDGGMSEVVQKQFQLNQRDEFIKAFVSEAIAKVVQPLTGKSEAQSPIDERDEIKDKGRKS ... ...LYTEQDSERVLARLRQRVRGFIPASDVVAIAANPQPVTLENGQLCQPEPEILPLIRRLAAVLRAEGEELIADNILLQSQRLGQEARHILDKQRRREAEKVVERFQWIG...YTMGLFGKSRKRPGKGRLEPKAPEVKTEAAEETLKAVRQQVKQIQDEVSRQAMLRRSEEIEAILSRGELLVVVFGTGSAGKTSLVNALIGRMVGQVGAPMGTTEVGETYKLKLKGLERPILITDTPGIL...inding protein domain protein Moorea producens 3L MPLPRLLTLIIGLIIILGLMLWLINGLYQLYIQISFTAPLLANLLLLLVITLLGLLIWALI

  18. High quality protein microarray using in situ protein purification

    Directory of Open Access Journals (Sweden)

    Fleischmann Robert D

    2009-08-01

    Full Text Available Abstract Background In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC. This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. Results Two slide surfaces were examined, chelated Cu2+ slides suspended on a polyethylene glycol (PEG coating and chelated Ni2+ slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu2+ slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents

  19. Predicting multiplex subcellular localization of proteins using protein-protein interaction network: a comparative study

    OpenAIRE

    Jiang Jonathan Q; Wu Maoying

    2012-01-01

    Abstract Background Proteins that interact in vivo tend to reside within the same or "adjacent" subcellular compartments. This observation provides opportunities to reveal protein subcellular localization in the context of the protein-protein interaction (PPI) network. However, so far, only a few efforts based on heuristic rules have been made in this regard. Results We systematically and quantitatively validate the hypothesis that proteins physically interacting with each other probably shar...

  20. Photolytic Crosslinking to Probe Protein-Protein and Protein-Matrix Interactions In Lyophilized Powders

    OpenAIRE

    Iyer, Lavanya K.; Moorthy, Balakrishnan S.; Topp, Elizabeth M.

    2015-01-01

    Protein structure and local environment in lyophilized formulations were probed using high-resolution solid-state photolytic crosslinking with mass spectrometric analysis (ssPC-MS). In order to characterize structure and microenvironment, protein-protein, protein-excipient and protein-water interactions in lyophilized powders were identified. Myoglobin (Mb) was derivatized in solution with the heterobifunctional probe succinimidyl 4,4’-azipentanoate (SDA) and the structural integrity of the l...

  1. Dairy Proteins and Energy Balance

    DEFF Research Database (Denmark)

    Bendtsen, Line Quist

    High protein diets affect energy balance beneficially through decreased hunger, enhanced satiety and increased energy expenditure. Dairy products are a major source of protein. Dairy proteins are comprised of two classes, casein (80%) and whey proteins (20%), which are both of high quality, but...... casein is absorbed slowly and whey is absorbed rapidly. The present PhD study investigated the effects of total dairy proteins, whey, and casein, on energy balance and the mechanisms behind any differences in the effects of the specific proteins. The results do not support the hypothesis that dairy...... proteins, whey or casein are more beneficial than other protein sources in the regulation of energy balance, and suggest that dairy proteins, whey or casein seem to play only a minor role, if any, in the prevention and treatment of obesity....

  2. Coevolution study of mitochondria respiratory chain proteins:Toward the understanding of protein-protein interaction

    Institute of Scientific and Technical Information of China (English)

    Ming Yang; Yan Ge; Jiayan Wu; Jingfa Xiao; Jun Yu

    2011-01-01

    Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein-protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using "Mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein-protein interaction in intra-complex and the binary protein-protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value = 4.4 x 10-6). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein-protein interaction.Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study.

  3. Protein-protein interaction databases: keeping up with growing interactomes

    Directory of Open Access Journals (Sweden)

    Lehne Benjamin

    2009-04-01

    Full Text Available Abstract Over the past few years, the number of known protein-protein interactions has increased substantially. To make this information more readily available, a number of publicly available databases have set out to collect and store protein-protein interaction data. Protein-protein interactions have been retrieved from six major databases, integrated and the results compared. The six databases (the Biological General Repository for Interaction Datasets [BioGRID], the Molecular INTeraction database [MINT], the Biomolecular Interaction Network Database [BIND], the Database of Interacting Proteins [DIP], the IntAct molecular interaction database [IntAct] and the Human Protein Reference Database [HPRD] differ in scope and content; integration of all datasets is non-trivial owing to differences in data annotation. With respect to human protein-protein interaction data, HPRD seems to be the most comprehensive. To obtain a complete dataset, however, interactions from all six databases have to be combined. To overcome this limitation, meta-databases such as the Agile Protein Interaction Database (APID offer access to integrated protein-protein interaction datasets, although these also currently have certain restrictions.

  4. Direct Probing of Protein-Protein Interactions

    International Nuclear Information System (INIS)

    This project aimed to establish feasibility of using experimental techniques based on direct measurements of interaction forces on the single molecule scale to characterize equilibrium interaction potentials between individual biological molecules. Such capability will impact several research areas, ranging from rapid interaction screening capabilities to providing verifiable inputs for computational models. It should be one of the enabling technologies for modern proteomics research. This study used a combination of Monte-Carlo simulations, theoretical considerations, and direct experimental measurements to investigate two model systems that represented typical experimental situations: force-induced melting of DNA rigidly attached to the tip, and force-induced unbinding of a protein-antibody pair connected to flexible tethers. Our results establish that for both systems researchers can use force spectroscopy measurements to extract reliable information about equilibrium interaction potentials. However, the approaches necessary to extract these potentials in each case--Jarzynski reconstruction and Dynamic Force Spectroscopy--are very different. We also show how the thermodynamics and kinetics of unbinding process dictates the choice between in each case

  5. Direct Probing of Protein-Protein Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Noy, A; Sulchek, T A; Friddle, R W

    2005-03-10

    This project aimed to establish feasibility of using experimental techniques based on direct measurements of interaction forces on the single molecule scale to characterize equilibrium interaction potentials between individual biological molecules. Such capability will impact several research areas, ranging from rapid interaction screening capabilities to providing verifiable inputs for computational models. It should be one of the enabling technologies for modern proteomics research. This study used a combination of Monte-Carlo simulations, theoretical considerations, and direct experimental measurements to investigate two model systems that represented typical experimental situations: force-induced melting of DNA rigidly attached to the tip, and force-induced unbinding of a protein-antibody pair connected to flexible tethers. Our results establish that for both systems researchers can use force spectroscopy measurements to extract reliable information about equilibrium interaction potentials. However, the approaches necessary to extract these potentials in each case--Jarzynski reconstruction and Dynamic Force Spectroscopy--are very different. We also show how the thermodynamics and kinetics of unbinding process dictates the choice between in each case.

  6. Hydrogels Constructed from Engineered Proteins.

    Science.gov (United States)

    Li, Hongbin; Kong, Na; Laver, Bryce; Liu, Junqiu

    2016-02-24

    Due to their various potential biomedical applications, hydrogels based on engineered proteins have attracted considerable interest. Benefitting from significant progress in recombinant DNA technology and protein engineering/design techniques, the field of protein hydrogels has made amazing progress. The latest progress of hydrogels constructed from engineered recombinant proteins are presented, mainly focused on biorecognition-driven physical hydrogels as well as chemically crosslinked hydrogels. The various bio-recognition based physical crosslinking strategies are discussed, as well as chemical crosslinking chemistries used to engineer protein hydrogels, and protein hydrogels' various biomedical applications. The future perspectives of this fast evolving field of biomaterials are also discussed. PMID:26707834

  7. Mapping the human protein interactome

    Institute of Scientific and Technical Information of China (English)

    Daniel Figeys

    2008-01-01

    Interactions are the essence of all biomolecules because they cannot fulfill their roles without interacting with other molecules. Hence, mapping the interactions of biomolecules can be useful for understanding their roles and functions. Furthermore, the development of molecular based systems biology requires an understanding of the biomolecular interactions. In recent years, the mapping of protein-protein interactions in different species has been reported, but few reports have focused on the large-scale mapping of protein-protein interactions in human. Here, we review the developments in protein interaction mapping and we discuss issues and strategies for the mapping of the human protein interactome.

  8. Affinity purification of proteins binding to GST fusion proteins.

    Science.gov (United States)

    Swaffield, J C; Johnston, S A

    2001-05-01

    This unit describes the use of proteins fused to glutathione-S-transferase (GST fusion proteins) to affinity purify other proteins, a technique also known as GST pulldown purification. The describes a strategy in which a GST fusion protein is bound to agarose affinity beads and the complex is then used to assay the binding of a specific test protein that has been labeled with [35S]methionine by in vitro translation. However, this method can be adapted for use with other types of fusion proteins; for example, His6, biotin tags, or maltose-binding protein fusions (MBP), and these may offer particular advantages. A describes preparation of an E. coli extract that is added to the reaction mixture with purified test protein to reduce nonspecific binding. PMID:18265191

  9. Functionalizing Microporous Membranes for Protein Purification and Protein Digestion

    Science.gov (United States)

    Dong, Jinlan; Bruening, Merlin L.

    2015-07-01

    This review examines advances in the functionalization of microporous membranes for protein purification and the development of protease-containing membranes for controlled protein digestion prior to mass spectrometry analysis. Recent studies confirm that membranes are superior to bead-based columns for rapid protein capture, presumably because convective mass transport in membrane pores rapidly brings proteins to binding sites. Modification of porous membranes with functional polymeric films or TiO2 nanoparticles yields materials that selectively capture species ranging from phosphopeptides to His-tagged proteins, and protein-binding capacities often exceed those of commercial beads. Thin membranes also provide a convenient framework for creating enzyme-containing reactors that afford control over residence times. With millisecond residence times, reactors with immobilized proteases limit protein digestion to increase sequence coverage in mass spectrometry analysis and facilitate elucidation of protein structures. This review emphasizes the advantages of membrane-based techniques and concludes with some challenges for their practical application.

  10. Protein-protein interactions in DNA mismatch repair.

    Science.gov (United States)

    Friedhoff, Peter; Li, Pingping; Gotthardt, Julia

    2016-02-01

    The principal DNA mismatch repair proteins MutS and MutL are versatile enzymes that couple DNA mismatch or damage recognition to other cellular processes. Besides interaction with their DNA substrates this involves transient interactions with other proteins which is triggered by the DNA mismatch or damage and controlled by conformational changes. Both MutS and MutL proteins have ATPase activity, which adds another level to control their activity and interactions with DNA substrates and other proteins. Here we focus on the protein-protein interactions, protein interaction sites and the different levels of structural knowledge about the protein complexes formed with MutS and MutL during the mismatch repair reaction. PMID:26725162

  11. How do oncoprotein mutations rewire protein-protein interaction networks?

    Science.gov (United States)

    Bowler, Emily H; Wang, Zhenghe; Ewing, Rob M

    2015-01-01

    The acquisition of mutations that activate oncogenes or inactivate tumor suppressors is a primary feature of most cancers. Mutations that directly alter protein sequence and structure drive the development of tumors through aberrant expression and modification of proteins, in many cases directly impacting components of signal transduction pathways and cellular architecture. Cancer-associated mutations may have direct or indirect effects on proteins and their interactions and while the effects of mutations on signaling pathways have been widely studied, how mutations alter underlying protein-protein interaction networks is much less well understood. Systematic mapping of oncoprotein protein interactions using proteomics techniques as well as computational network analyses is revealing how oncoprotein mutations perturb protein-protein interaction networks and drive the cancer phenotype. PMID:26325016

  12. Geometric De-noising of Protein-Protein Interaction Networks

    OpenAIRE

    Kuchaiev, Oleksii; Rasajski, Marija; Higham, Desmond J.; Przul, Natasa; Przytycka, Teresa Maria

    2009-01-01

    Understanding complex networks of protein-protein interactions (PPIs) is one of the foremost challenges of the post-genomic era. Due to the recent advances in experimental bio-technology, including yeast-2-hybrid (Y2H), tandem affinity purification (TAP) and other high-throughput methods for protein-protein interaction (PPI) detection, huge amounts of PPI network data are becoming available. Of major concern, however, are the levels of noise and incompleteness. For example, for Y2H screens, i...

  13. Cooperative long range protein-protein dynamics in Purple Membrane

    OpenAIRE

    Rheinstadter, Maikel; Schmalzl, Karin; Wood, Kathleen; Strauch, Dieter

    2008-01-01

    We present experimental evidence for a long-range protein-protein interaction in purple membrane (PM). The interprotein dynamics were quantified by measuring the spectrum of the acoustic phonons in the 2D bacteriorhodopsin (BR) protein lattice using inelastic neutron scattering. Phonon energies of about 1 meV were determined. The data are compared to an analytical model, and the effective spring constant for the interaction between neighboring protein trimers are determined to be k=53 N/m. Ad...

  14. Biophysics of protein evolution and evolutionary protein biophysics

    OpenAIRE

    Sikosek, Tobias; Chan, Hue Sun

    2014-01-01

    The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for ...

  15. Statistical thermodynamics of membrane bending mediated protein-protein attraction

    OpenAIRE

    Chou, Tom; Kim, Ken S.; Oster, George

    1999-01-01

    Integral membrane proteins deform the surrounding bilayer creating long-ranged forces that influence distant proteins. These forces can be attractive or repulsive, depending on the proteins' shape, height, contact angle with the bilayer, as well as the local membrane curvature. Although interaction energies are not pairwise additive, for sufficiently low protein density, thermodynamic properties depend only upon pair interactions. Here, we compute pair interaction potentials and entropic cont...

  16. Conformational Analysis of Therapeutic Proteins by Hydroxyl Radical Protein Footprinting

    OpenAIRE

    Watson, Caroline; Sharp, Joshua S.

    2012-01-01

    Unlike small molecule drugs, therapeutic protein pharmaceuticals must not only have the correct amino acid sequence and modifications, but also the correct conformation to ensure safety and efficacy. Here, we describe a method for comparison of therapeutic protein conformations by hydroxyl radical protein footprinting using liquid chromatography-mass spectrometry (LC-MS) as an analytical platform. Hydroxyl radical protein footprinting allows for rapid analysis of the conformation of therapeut...

  17. Hub Promiscuity in Protein-Protein Interaction Networks

    OpenAIRE

    Haruki Nakamura; Kengo Kinoshita; Ashwini Patil

    2010-01-01

    Hubs are proteins with a large number of interactions in a protein-protein interaction network. They are the principal agents in the interaction network and affect its function and stability. Their specific recognition of many different protein partners is of great interest from the structural viewpoint. Over the last few years, the structural properties of hubs have been extensively studied. We review the currently known features that are particular to hubs, possibly affecting their binding ...

  18. Metabolism of minor isoforms of prion proteins Cytosolic prion protein and transmembrane prion protein*

    Institute of Scientific and Technical Information of China (English)

    Zhiqi Song; Deming Zhao; Lifeng Yang

    2013-01-01

    Transmissible spongiform encephalopathy or prion disease is triggered by the conversion from cellular prion protein to pathogenic prion protein. Growing evidence has concentrated on prion protein configuration changes and their correlation with prion disease transmissibility and pathoge-nicity. In vivo and in vitro studies have shown that several cytosolic forms of prion protein with spe-cific topological structure can destroy intracellular stability and contribute to prion protein pathoge-nicity. In this study, the latest molecular chaperone system associated with endoplasmic reticu-lum-associated protein degradation, the endoplasmic reticulum resident protein quality-control system and the ubiquitination proteasome system, is outlined. The molecular chaperone system directly correlates with the prion protein degradation pathway. Understanding the molecular me-chanisms wil help provide a fascinating avenue for further investigations on prion disease treatment and prion protein-induced neurodegenerative diseases.

  19. Protein Functionalized Nanodiamond Arrays

    Directory of Open Access Journals (Sweden)

    Liu YL

    2010-01-01

    Full Text Available Abstract Various nanoscale elements are currently being explored for bio-applications, such as in bio-images, bio-detection, and bio-sensors. Among them, nanodiamonds possess remarkable features such as low bio-cytotoxicity, good optical property in fluorescent and Raman spectra, and good photostability for bio-applications. In this work, we devise techniques to position functionalized nanodiamonds on self-assembled monolayer (SAMs arrays adsorbed on silicon and ITO substrates surface using electron beam lithography techniques. The nanodiamond arrays were functionalized with lysozyme to target a certain biomolecule or protein specifically. The optical properties of the nanodiamond-protein complex arrays were characterized by a high throughput confocal microscope. The synthesized nanodiamond-lysozyme complex arrays were found to still retain their functionality in interacting with E. coli.

  20. A magnetic protein biocompass

    Science.gov (United States)

    Qin, Siying; Yin, Hang; Yang, Celi; Dou, Yunfeng; Liu, Zhongmin; Zhang, Peng; Yu, He; Huang, Yulong; Feng, Jing; Hao, Junfeng; Hao, Jia; Deng, Lizong; Yan, Xiyun; Dong, Xiaoli; Zhao, Zhongxian; Jiang, Taijiao; Wang, Hong-Wei; Luo, Shu-Jin; Xie, Can

    2016-02-01

    The notion that animals can detect the Earth’s magnetic field was once ridiculed, but is now well established. Yet the biological nature of such magnetosensing phenomenon remains unknown. Here, we report a putative magnetic receptor (Drosophila CG8198, here named MagR) and a multimeric magnetosensing rod-like protein complex, identified by theoretical postulation and genome-wide screening, and validated with cellular, biochemical, structural and biophysical methods. The magnetosensing complex consists of the identified putative magnetoreceptor and known magnetoreception-related photoreceptor cryptochromes (Cry), has the attributes of both Cry- and iron-based systems, and exhibits spontaneous alignment in magnetic fields, including that of the Earth. Such a protein complex may form the basis of magnetoreception in animals, and may lead to applications across multiple fields.

  1. Markers of protein oxidation

    DEFF Research Database (Denmark)

    Headlam, Henrietta A; Davies, Michael Jonathan

    2004-01-01

    Exposure of proteins to radicals in the presence of O2 gives both side-chain oxidation and backbone fragmentation. These processes can be interrelated, with initial side-chain oxidation giving rise to backbone damage via transfer reactions. We have shown previously that alkoxyl radicals formed...... on the C-3 carbons of Ala, Val, Leu, and Asp residues undergo beta-scission to give backbone alpha-carbon radicals, with the release of the side- chain as a carbonyl compound. We now show that this is a general mechanism that occurs with a wide range of oxidants. The quantitative significance...... of this process depends on the extent of oxidation at C-3 compared with other sites. HO*, generated by gamma radiolysis, gave the highest total carbonyl yield, with protein-bound carbonyls predominating over released. In contrast, metal ion/H2O2 systems, gave more released than bound carbonyls, with this ratio...

  2. Yeast Interacting Proteins Database: YJL199C, YJL199C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available d in closely related Saccharomyces species; protein detected in large-scale protein-protein interaction studies...cies; protein detected in large-scale protein-protein interaction studies Rows with this prey as prey (4) Ro...n; not conserved in closely related Saccharomyces species; protein detected in large-scale protein-protein interaction studies... species; protein detected in large-scale protein-protein interaction studies Rows with this prey as prey Ro

  3. High throughput recombinant protein production of fungal secreted proteins

    DEFF Research Database (Denmark)

    Vala, Andrea Lages Lino; Roth, Doris; Grell, Morten Nedergaard;

    2011-01-01

    high-throughput protein production system with a special focus on fungal secreted proteins. We use a ligation independent cloning to clone target genes into expression vectors for E. coli and P. pastoris and a small scale test expression to identify constructs producing soluble protein. Expressed...

  4. Protein Crystal Isocitrate Lyase

    Science.gov (United States)

    1998-01-01

    The comparison of protein crystal, Isocitrate Lyase earth-grown (left) and space-grown (right). This is a target enzyme for fungicides. A better understanding of this enzyme should lead to the discovery of more potent fungicides to treat serious crop diseases such as rice blast; it regulates the flow of metabolic intermediates required for cell growth. Principal Investigator is Larry DeLucas.

  5. HRTEM in protein crystallography

    International Nuclear Information System (INIS)

    Electron microscopy/diffraction (ED/D) using spot-scan and low-dose imaging has been successfully applied to investigate microcrystals of an alpha-helical coiled-coil protein extracted from ootheca of the praying mantis. Fourier transforms of the images show resolution out to 4 Angstroems and can be used to phase the corresponding ED data which shows reflections out to 2 Aangstroems. 5 refs., 3 figs

  6. Proteins, electrochemical detection of

    Czech Academy of Sciences Publication Activity Database

    Bartošík, Martin; Doneux, T.; Pechan, Zdeněk; Ostatná, Veronika; Paleček, Emil

    Chichester : John Wiley & Sons Ltd, 2009 - (Meyers, R.), s. 1-37 ISBN 978-0-470-97333-2 R&D Projects: GA AV ČR(CZ) KAN400310651; GA MŠk(CZ) LC06035 Grant ostatní: GA ČR(CZ) GA301/07/0490 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : protein electrochemistry * electrodes - carbon * gold Subject RIV: BO - Biophysics

  7. Tuber Storage Proteins

    OpenAIRE

    Shewry, Peter R.

    2003-01-01

    A wide range of plants are grown for their edible tubers, but five species together account for almost 90 % of the total world production. These are potato (Solanum tuberosum), cassava (Manihot esculenta), sweet potato (Ipomoea batatus), yams (Dioscorea spp.) and taro (Colocasia, Cyrtosperma and Xanthosoma spp.). All of these, except cassava, contain groups of storage proteins, but these differ in the biological properties and evolutionary relationships. Thus, patatin from potato exhibits act...

  8. Protein aggregation and bioprocessing

    OpenAIRE

    Cromwell, Mary E. M.; Hilario, Eric; Jacobson, Fred

    2006-01-01

    Protein aggregation is a common issue encountered during manufacture of biotherapeutics. It is possible to influence the amount of aggregate produced during the cell culture and purification process by carefully controlling the environment (eg, media components) and implementing appro-priate strategies to minimize the extent of aggregation. Steps to remove aggregates have been successfully used at a manufacturing scale. Care should be taken when developing a process to monitor the compatibili...

  9. PEGylation of therapeutic proteins

    OpenAIRE

    Jevsevar, Simona; Kunstelj, Menci; Gaberc Porekar, Vladka

    2010-01-01

    Abstract PEGylation has been widely used as a post-production modification methodology for improving biomedical efficacy and physicochemical properties of therapeutic proteins since the first PEGylated product was approved by Food and Drug Administration in 1990. Applicability and safety of this technology have been proven by use of various PEGylated pharmaceuticals for many years. It is expected that PEGylation as the most established technology for extension of drug residence in ...

  10. DELIVERY OF THERAPEUTIC PROTEINS

    OpenAIRE

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2010-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanop...

  11. Protein threading by learning

    Science.gov (United States)

    Chang, Iksoo; Cieplak, Marek; Dima, Ruxandra I.; Maritan, Amos; Banavar, Jayanth R.

    2001-01-01

    By using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems. PMID:11717394

  12. Redox meets protein trafficking.

    Science.gov (United States)

    Bölter, Bettina; Soll, Jürgen; Schwenkert, Serena

    2015-09-01

    After the engulfment of two prokaryotic organisms, the thus emerged eukaryotic cell needed to establish means of communication and signaling to properly integrate the acquired organelles into its metabolism. Regulatory mechanisms had to evolve to ensure that chloroplasts and mitochondria smoothly function in accordance with all other cellular processes. One essential process is the post-translational import of nuclear encoded organellar proteins, which needs to be adapted according to the requirements of the plant. The demand for protein import is constantly changing depending on varying environmental conditions, as well as external and internal stimuli or different developmental stages. Apart from long-term regulatory mechanisms such as transcriptional/translation control, possibilities for short-term acclimation are mandatory. To this end, protein import is integrated into the cellular redox network, utilizing the recognition of signals from within the organelles and modifying the efficiency of the translocon complexes. Thereby, cellular requirements can be communicated throughout the whole organism. This article is part of a Special Issue entitled: Chloroplast Biogenesis. PMID:25626173

  13. Neutron protein crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Niimura, Nobuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-10-01

    X-ray diffraction of single crystal has enriched the knowledge of various biological molecules such as proteins, DNA, t-RNA, viruses, etc. It is difficult to make structural analysis of hydrogen atoms in a protein using X-ray crystallography, whereas neutron diffraction seems usable to directly determine the location of those hydrogen atoms. Here, neutron diffraction method was applied to structural analysis of hen egg-white lysozyme. Since the crystal size of a protein to analyze is generally small (5 mm{sup 3} at most), the neutron beam at the sample position in monochromator system was set to less than 5 x 5 mm{sup 2} and beam divergence to 0.4 degree or less. Neutron imaging plate with {sup 6}Li or Gd mixed with photostimulated luminescence material was used and about 2500 Bragg reflections were recorded in one crystal setting. A total of 38278 reflections for 2.0 A resolution were collected in less than 10 days. Thus, stereo views of Trp-111 omit map around the indol ring of Trp-111 was presented and the three-dimensional arrangement of 696H and 264D atoms in the lysozyme molecules was determined using the omit map. (M.N.)

  14. Protein Misfolding and Human Disease

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter Gerd; Vang, Søren; Christensen, Jane Hvarregaard

    2006-01-01

    Protein misfolding is a common event in living cells. In young and healthy cells, the misfolded protein load is disposed of by protein quality control (PQC) systems. In aging cells and in cells from certain individuals with genetic diseases, the load may overwhelm the PQC capacity, resulting in...... accumulation of misfolded proteins. Dependent on the properties of the protein and the efficiency of the PQC systems, the accumulated protein may be degraded or assembled into toxic oligomers and aggregates. To illustrate this concept, we discuss a number of very different protein misfolding diseases including...... phenylketonuria, Parkinson's disease, α-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute...

  15. Protein: FBA4 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FBA4 general transcription factor TFIIH ERCC3 XPB, XPBC ERCC3 TFIIH basal transcription factor c ... bunit Basic transcription factor 2 89 kDa subunit, DNA ... excision repair protein ERCC-3, DNA ... repair protein ...

  16. Protein: FBA4 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FBA4 general transcription factor TFIIH ERCC2 XPD, XPDC ERCC2_gene TFIIH basal transcription fac ... Basic transcription factor 2 80 kDa subunit, CXPD, DNA ... excision repair protein ERCC-2, DNA ... repair protein ...

  17. Dipolar response of hydrated proteins

    CERN Document Server

    Matyushov, Dmitry V

    2011-01-01

    The paper presents an analytical theory and numerical simulations of the dipolar response of hydrated proteins. The effective dielectric constant of the solvated protein, representing the average dipole moment induced at the protein by a uniform external field, shows a remarkable variation among the proteins studied by numerical simulations. It changes from 0.5 for ubiquitin to 640 for cytochrome c. The former value implies a negative dipolar susceptibility of ubiquitin, that is a dia-electric dipolar response and negative dielectrophoresis. It means that a protein carrying an average dipole of ~240 D is expected to repel from the region of a stronger electric field. This outcome is the result of a negative cross-correlation between the protein and water dipoles, compensating for the positive variance of the protein dipole in the overall dipolar susceptibility. This phenomenon can be characterized as overscreening of protein's dipole by the hydration shell. In contrast to the neutral ubiquitin, charged protei...

  18. Leptospira Protein Expression During Infection

    Science.gov (United States)

    We are characterizing protein expression in vivo during experimental leptospirosis using immunofluorescence microscopy. Coding regions for several proteins were identified through analysis of Leptospira interrogans serovar Copenhageni and L. borgpetersenii serovar Hardjo genomes. In addition, codi...

  19. Stabilized polyacrylic saccharide protein conjugates

    Science.gov (United States)

    Callstrom, M.R.; Bednarski, M.D.; Gruber, P.R.

    1996-02-20

    This invention is directed to water soluble protein polymer conjugates which are stable in hostile environments. The conjugate comprises a protein which is linked to an acrylic polymer at multiple points through saccharide linker groups. 16 figs.

  20. Protein: FEA6 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FEA6 Histone Deacetylases BRD2 KIAA9001, RING3 BRD2 Bromodomain-containing protein 2 O27.1.1, Re ... ally interesting new ... gene 3 protein 9606 Homo sapiens P25440 6046 3ONI, ...

  1. Protein: MPB2 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available MPB2 Transcription regulators NCOA3 AIB1, BHLHE42, RAC3, TRAM1 NCOA3 Nuclear receptor coactivato ... r 3 ACTR, Amplified in breast cancer ... 1 protein, CBP-interacting protein, Class E basic ...

  2. Lattice tube model of proteins

    OpenAIRE

    Banavar, Jayanth R.; Cieplak, Marek; Maritan, Amos

    2004-01-01

    We present a new lattice model for proteins that incorporates a tube-like anisotropy by introducing a preference for mutually parallel alignments in the conformations. The model is demonstrated to capture many aspects of real proteins.

  3. Lattice Tube Model of Proteins

    Science.gov (United States)

    Banavar, Jayanth R.; Cieplak, Marek; Maritan, Amos

    2004-11-01

    We present a new lattice model for proteins that incorporates a tubelike anisotropy by introducing a preference for mutually parallel alignments in the conformations. The model is demonstrated to capture many aspects of real proteins.

  4. Geometry and physics of proteins

    Science.gov (United States)

    Banavar, Jayanth R.; Cieplak, Marek; Hoang, Trinh X.; Maritan, Amos

    2005-03-01

    We recall some of the key lessons of protein research over the last several decades and show that they strongly suggest a new framework for understanding proteins. The unified framework is useful for understanding protein folding, amyloid formation and protein interactions and has important implications for natural selection. The experimental data and our new approach, supported by computer simulations, reveal an astonishing simplicity underlying the protein problem. REFERENCES: Banavar, J. R. and Maritan, A. (2003). Colloquium: Geometrical approach to protein folding: A tube picture. Rev. Mod. Phys. 75, 23. Banavar, J. R., Hoang, T. X., Maritan, A., Seno, F. and Trovato, A., (2004). A unified perspective on proteins -- a physics approach. Phys. Rev. E 70, 041905. Banavar, J. R., Cieplak, M. and Maritan, A., (2004). Lattice tube model of proteins, Phys. Rev. Lett. (in press).

  5. Protein: FBA5 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FBA5 VSOP(voltage sensor -only protein1) HVCN1 VSOP, VSX1 Voltage-gated hydrogen channel 1 Hydrog ... en voltage-gated channel 1, Voltage sensor ... domain-only protein 7719 Ciona intestinalis 778897 ...

  6. Protein Linked to Atopic Dermatitis

    Science.gov (United States)

    ... Research Matters NIH Research Matters January 14, 2013 Protein Linked to Atopic Dermatitis Normal skin from a ... in mice suggests that lack of a certain protein may trigger atopic dermatitis, the most common type ...

  7. Protein: MPA1 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available MPA1 TLR signaling molecules Mavs Ips1, Visa Mitochondrial antiviral-signaling protein CARD adap ... ta, Interferon beta promoter stimulator protein 1, Virus -induced-signaling adapter 10090 Mus musculus 22860 ...

  8. Yeast Interacting Proteins Database: YNL086W, YKL061W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YNL086W - Putative protein of unknown function; green ... fluorescent protein (GFP)-fusion protein l ... 2) YKL061W - Putative protein of unknown function; green ... fluorescent protein (GFP)-fusion protein localizes ... description Putative protein of unknown function; green ... fluorescent protein (GFP)-fusion protein localizes ...

  9. Yeast Interacting Proteins Database: YLR108C, YLR108C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YLR108C - Protein of unknown function; green ... fluorescent protein (GFP)-fusion protein localizes ... as prey (1) YLR108C - Protein of unknown function; green ... fluorescent protein (GFP)-fusion protein localizes ... me - Bait description Protein of unknown function; green ... fluorescent protein (GFP)-fusion protein localizes ...

  10. Yeast Interacting Proteins Database: YJR056C, YJR056C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YJR056C - Putative protein of unknown function; green ... fluorescent protein (GFP)-fusion protein l ... 2) YJR056C - Putative protein of unknown function; green ... fluorescent protein (GFP)-fusion protein localizes ... description Putative protein of unknown function; green ... fluorescent protein (GFP)-fusion protein localizes ...

  11. Protein kinase substrate identification on functional protein arrays

    Directory of Open Access Journals (Sweden)

    Zhou Fang

    2008-02-01

    Full Text Available Abstract Background Over the last decade, kinases have emerged as attractive therapeutic targets for a number of different diseases, and numerous high throughput screening efforts in the pharmaceutical community are directed towards discovery of compounds that regulate kinase function. The emerging utility of systems biology approaches has necessitated the development of multiplex tools suitable for proteomic-scale experiments to replace lower throughput technologies such as mass spectroscopy for the study of protein phosphorylation. Recently, a new approach for identifying substrates of protein kinases has applied the miniaturized format of functional protein arrays to characterize phosphorylation for thousands of candidate protein substrates in a single experiment. This method involves the addition of protein kinases in solution to arrays of immobilized proteins to identify substrates using highly sensitive radioactive detection and hit identification algorithms. Results To date, the factors required for optimal performance of protein array-based kinase substrate identification have not been described. In the current study, we have carried out a detailed characterization of the protein array-based method for kinase substrate identification, including an examination of the effects of time, buffer compositions, and protein concentration on the results. The protein array approach was compared to standard solution-based assays for assessing substrate phosphorylation, and a correlation of greater than 80% was observed. The results presented here demonstrate how novel substrates for protein kinases can be quickly identified from arrays containing thousands of human proteins to provide new clues to protein kinase function. In addition, a pooling-deconvolution strategy was developed and applied that enhances characterization of specific kinase-substrate relationships and decreases reagent consumption. Conclusion Functional protein microarrays are an

  12. From protein engineering to immobilization

    DEFF Research Database (Denmark)

    Singh, Raushan Kumar; Tiwari, Manish Kumar; Singh, Ranjitha; Lee, Jung-Kul

    2013-01-01

    in protein engineering have revolutionized the development of commercially available enzymes into better industrial catalysts. Protein engineering aims at modifying the sequence of a protein, and hence its structure, to create enzymes with improved functional properties such as stability, specific...... in improved enzyme stability. Protein engineering and immobilization techniques are sequential and compatible approaches for the improvement of enzyme properties. The present review highlights and summarizes various studies that have aimed to improve the biochemical properties of industrially...

  13. Spectral affinity in protein networks

    OpenAIRE

    Teng Shang-Hua; Voevodski Konstantin; Xia Yu

    2009-01-01

    Abstract Background Protein-protein interaction (PPI) networks enable us to better understand the functional organization of the proteome. We can learn a lot about a particular protein by querying its neighborhood in a PPI network to find proteins with similar function. A spectral approach that considers random walks between nodes of interest is particularly useful in evaluating closeness in PPI networks. Spectral measures of closeness are more robust to noise in the data and are more precise...

  14. Protein structure by mechanical triangulation

    OpenAIRE

    Dietz, Hendrik; Rief, Matthias

    2006-01-01

    Knowledge of protein structure is essential to understand protein function. High-resolution protein structure has so far been the domain of ensemble methods. Here, we develop a simple single-molecule technique to measure spatial position of selected residues within a folded and functional protein structure in solution. Construction and mechanical unfolding of cysteine-engineered polyproteins with controlled linkage topology allows measuring intramolecular distance with angstrom precision. We ...

  15. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformations...... synthetic example from molecular dynamics simulations. We then apply the algorithms to revisit the problem of ensemble averaging during structure determination of proteins, and find that an ensemble refinement method is able to recover the correct distribution of conformations better than standard single...

  16. Green fluorescent protein: A perspective

    OpenAIRE

    Remington, S James

    2011-01-01

    A brief personal perspective is provided for green fluorescent protein (GFP), covering the period 1994–2011. The topics discussed are primarily those in which my research group has made a contribution and include structure and function of the GFP polypeptide, the mechanism of fluorescence emission, excited state protein transfer, the design of ratiometric fluorescent protein biosensors and an overview of the fluorescent proteins derived from coral reef animals. Structure-function relationship...

  17. Recent advances of protein microarrays

    OpenAIRE

    Hultschig, Claus; Kreutzberger, Jürgen; Seitz, Harald; Konthur, Zoltán; Büssow, Konrad; Lehrach, Hans

    2006-01-01

    Technological innovations and novel applications have greatly advanced the field of protein microarrays. Over the past two years, different types of protein microarrays have been used for serum profiling, protein abundance determinations, and identification of proteins that bind DNA or small compounds. However, considerable development is still required to ensure common quality standards and to establish large content repertoires. Here, we summarize applications available to date and discuss ...

  18. Putting Proteins back into Water

    OpenAIRE

    Rios, Paolo De Los; Caldarelli, Guido

    2000-01-01

    We introduce a simplified protein model where the solvent (water) degrees of freedom appear explicitly (although in an extremely simplified fashion). Using this model we are able to recover the thermodynamic phenomenology of proteins over a wide range of temperatures. In particular we describe both the warm and the {\\it cold} protein denaturation within a single framework, while addressing important issues about the structure of model proteins.

  19. Charge configurations in viral proteins.

    OpenAIRE

    Karlin, S; Brendel, V

    1988-01-01

    The spatial distribution of the charged residues of a protein is of interest with respect to potential electrostatic interactions. We have examined the proteins of a large number of representative eukaryotic and prokaryotic viruses for the occurrence of significant clusters, runs, and periodic patterns of charge. Clusters and runs of positive charge are prominent in many capsid and core proteins, whereas surface (glyco)proteins frequently contain a negative charge cluster. Significant charge ...

  20. Protein: FBB5 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FBB5 RNA silencing RAN ARA24 Ran_(biology) GTP-binding nuclear ... protein Ran Androgen receptor-ass ... 24, GTPase Ran, Ras-like protein TC4, Ras-related nuclear ... protein 9606 Homo sapiens P62826 5901 1I2M, 3GJ4, ...

  1. Functional Foods Containing Whey Proteins

    Science.gov (United States)

    Whey proteins, modified whey proteins, and whey components are useful as nutrients or supplements for health maintenance. Extrusion modified whey proteins can easily fit into new products such as beverages, confectionery items (e.g., candies), convenience foods, desserts, baked goods, sauces, and in...

  2. Structural genomics of membrane proteins

    OpenAIRE

    Walian, Peter; Cross, Timothy A.; Jap, Bing K.

    2004-01-01

    Improvements in the fields of membrane-protein molecular biology and biochemistry, technical advances in structural data collection and processing, and the availability of numerous sequenced genomes have paved the way for membrane-protein structural genomics efforts. There has been significant recent progress, but various issues essential for high-throughput membrane-protein structure determination remain to be resolved.

  3. Protein: FBA6 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FBA6 vesicular transport COL4A3BP CERT, STAR D11 COL4A3BP Collagen type IV alpha-3-binding protei ... sfer protein, Goodpasture antigen-binding protein, STAR T domain-containing protein 11, StAR -related lipid ...

  4. BINDING ISOTHERMS SURFACTANT-PROTEINS

    OpenAIRE

    Elena Irina Moater; Cristiana Radulescu; Ionica Ionita

    2011-01-01

    The interactions between surfactants and proteins shows some similarities with interactions between surfactants and polymers, but the hydrophobic amphoteric nature of proteins and their secondary and tertiary structure components make them different from conventional polymer systems. Many studies from the past about surfactant - proteins bonding used the dialysis techniques. Other techniques used to determine the binding isotherm, included ultrafiltration, ultracentrifugation, potentiometry, ...

  5. Transient interactions between photosynthetic proteins

    NARCIS (Netherlands)

    Hulsker, Rinske

    2008-01-01

    The biological processes that are the basis of all life forms are mediated largely by protein-protein interactions. The protein complexes involved in these interactions can be categorised by their affinity, which results in a range from static to transient complexes. Electron transfer complexes, whi

  6. A model of tripeptidyl-peptidase I (CLN2, a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases

    Directory of Open Access Journals (Sweden)

    Oyama Hiroshi

    2003-11-01

    Full Text Available Abstract Background Tripeptidyl-peptidase I, also known as CLN2, is a member of the family of sedolisins (serine-carboxyl peptidases. In humans, defects in expression of this enzyme lead to a fatal neurodegenerative disease, classical late-infantile neuronal ceroid lipofuscinosis. Similar enzymes have been found in the genomic sequences of several species, but neither systematic analyses of their distribution nor modeling of their structures have been previously attempted. Results We have analyzed the presence of orthologs of human CLN2 in the genomic sequences of a number of eukaryotic species. Enzymes with sequences sharing over 80% identity have been found in the genomes of macaque, mouse, rat, dog, and cow. Closely related, although clearly distinct, enzymes are present in fish (fugu and zebra, as well as in frogs (Xenopus tropicalis. A three-dimensional model of human CLN2 was built based mainly on the homology with Pseudomonas sp. 101 sedolisin. Conclusion CLN2 is very highly conserved and widely distributed among higher organisms and may play an important role in their life cycles. The model presented here indicates a very open and accessible active site that is almost completely conserved among all known CLN2 enzymes. This result is somehow surprising for a tripeptidase where the presence of a more constrained binding pocket was anticipated. This structural model should be useful in the search for the physiological substrates of these enzymes and in the design of more specific inhibitors of CLN2.

  7. Involvement of the mitochondrial compartment in human NCL fibroblasts

    International Nuclear Information System (INIS)

    Highlights: ► Mitochondrial reticulum fragmentation occurs in human CLN1 and CLN6 fibroblasts. ► Likewise mitochondrial shift-to periphery and decreased mitochondrial density are seen. ► Enhanced caspase-mediated apoptosis occurs following STS treatment in CLN1 fibroblasts. -- Abstract: Neuronal ceroid lipofuscinosis (NCL) are a group of progressive neurodegenerative disorders of childhood, characterized by the endo-lysosomal storage of autofluorescent material. Impaired mitochondrial function is often associated with neurodegeneration, possibly related to the apoptotic cascade. In this study we investigated the possible effects of lysosomal accumulation on the mitochondrial compartment in the fibroblasts of two NCL forms, CLN1 and CLN6. Fragmented mitochondrial reticulum was observed in all cells by using the intravital fluorescent marker Mitotracker, mainly in the perinuclear region. This was also associated with intense signal from the lysosomal markers Lysotracker and LAMP2. Likewise, mitochondria appeared to be reduced in number and shifted to the cell periphery by electron microscopy; moreover the mitochondrial markers VDCA and COX IV were reduced following quantitative Western blot analysis. Whilst there was no evidence of increased cell death under basal condition, we observed a significant increase in apoptotic nuclei following Staurosporine treatment in CLN1 cells only. In conclusion, the mitochondrial compartment is affected in NCL fibroblasts invitro, and CLN1 cells seem to be more vulnerable to the negative effects of stressed mitochondrial membrane than CLN6 cells.

  8. Involvement of the mitochondrial compartment in human NCL fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Pezzini, Francesco; Gismondi, Floriana [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy); Tessa, Alessandra [IRCCS Fondazione Stella Maris-Molecular Medicine Unit, Pisa (Italy); Tonin, Paola [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy); Carrozzo, Rosalba [IRCCS Bambino Gesu Hospital-Molecular Medicine Unit, Roma (Italy); Mole, Sara E. [MRC Laboratory for Molecular Cell Biology, Molecular Medicines Unit, UCL Institute of Child Health and Department of Genetics, Evolution and Environment, University College London (United Kingdom); Santorelli, Filippo M. [IRCCS Fondazione Stella Maris-Molecular Medicine Unit, Pisa (Italy); Simonati, Alessandro, E-mail: alessandro.simonati@univr.it [Department of Neurological, Psychological, Morphological and Motor Sciences, Divisions of Neurology (Child Neurology) and Neuropathology, University of Verona Medical School, Verona (Italy)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Mitochondrial reticulum fragmentation occurs in human CLN1 and CLN6 fibroblasts. Black-Right-Pointing-Pointer Likewise mitochondrial shift-to periphery and decreased mitochondrial density are seen. Black-Right-Pointing-Pointer Enhanced caspase-mediated apoptosis occurs following STS treatment in CLN1 fibroblasts. -- Abstract: Neuronal ceroid lipofuscinosis (NCL) are a group of progressive neurodegenerative disorders of childhood, characterized by the endo-lysosomal storage of autofluorescent material. Impaired mitochondrial function is often associated with neurodegeneration, possibly related to the apoptotic cascade. In this study we investigated the possible effects of lysosomal accumulation on the mitochondrial compartment in the fibroblasts of two NCL forms, CLN1 and CLN6. Fragmented mitochondrial reticulum was observed in all cells by using the intravital fluorescent marker Mitotracker, mainly in the perinuclear region. This was also associated with intense signal from the lysosomal markers Lysotracker and LAMP2. Likewise, mitochondria appeared to be reduced in number and shifted to the cell periphery by electron microscopy; moreover the mitochondrial markers VDCA and COX IV were reduced following quantitative Western blot analysis. Whilst there was no evidence of increased cell death under basal condition, we observed a significant increase in apoptotic nuclei following Staurosporine treatment in CLN1 cells only. In conclusion, the mitochondrial compartment is affected in NCL fibroblasts invitro, and CLN1 cells seem to be more vulnerable to the negative effects of stressed mitochondrial membrane than CLN6 cells.

  9. The prevalence of nine genetic disorders in a dog population from Belgium, the Netherlands and Germany.

    Science.gov (United States)

    Broeckx, Bart J G; Coopman, Frank; Verhoeven, Geert E C; Van Haeringen, Wim; van de Goor, Leanne; Bosmans, Tim; Gielen, Ingrid; Saunders, Jimmy H; Soetaert, Sandra S A; Van Bree, Henri; Van Neste, Christophe; Van Nieuwerburgh, Filip; Van Ryssen, Bernadette; Verelst, Elien; Van Steendam, Katleen; Deforce, Dieter

    2013-01-01

    The objective of this study was to screen a dog population from Belgium, the Netherlands and Germany for the presence of mutant alleles associated with hip dysplasia (HD), degenerative myelopathy (DM), exercise-induced collapse (EIC), neuronal ceroid lipofuscinosis 4A (NCL), centronuclear myopathy (HMLR), mucopolysaccharidosis VII (MPS VII), myotonia congenita (MG), gangliosidosis (GM1) and muscular dystrophy (Duchenne type) (GRMD). Blood samples (K3EDTA) were collected for genotyping with Kompetitive Allele Specific PCR (n = 476). Allele and genotype frequencies were calculated in those breeds with at least 12 samples (n = 8). Hardy-Weinberg equilibrium was tested. Genetic variation was identified for 4 out of 9 disorders: mutant alleles were found in 49, 15, 3 and 2 breeds for HD, DM, EIC and NCL respectively. Additionally, mutant alleles were identified in crossbreeds for both HD and EIC. For HD, DM, EIC and NCL mutant alleles were newly discovered in 43, 13, 2 and 1 breed(s), respectively. In 9, 2 and 1 breed(s) for DM, EIC and NCL respectively, the mutant allele was detected, but the respective disorder has not been reported in those breeds. For 5 disorders (HMLR, MPS VII, MG, GM1, GRMD), the mutant allele could not be identified in our population. For the other 4 disorders (HD, DM, EIC, NCL), prevalence of associated mutant alleles seems strongly breed dependent. Surprisingly, mutant alleles were found in many breeds where the disorder has not been reported to date. PMID:24069350

  10. Peptidase Activities of Tripeptidyl Peptidase Ⅰ(TPP Ⅰ): Exopeptidase and Endopeptidase

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The defect of TPP Ⅰ causes a disease, late infantile neuronal ceroid lipofuscinosis(LINCL, CLN2). To investigate the bio-activity of tripeptidyl peptidase Ⅰ(TPP Ⅰ) from rat kidneys, the effects of digestion of angiotensin Ⅱ(Ang Ⅱ) and a synthetic endo-type substrate(Gly1-Lys-Pro-Iie-Pro5-Phe-Phe-Arg-Leu-Lys10) via TPP Ⅰ were analyzed by HPLC and TOF-MS. The data suggest that the degradation rate of Ang Ⅱ can reach 18.2% by the rat TPP Ⅰ and DRV(Asp-Arg-Val) can be released from N-termini of Ang Ⅱ within 16 h. In addition, the synthetic endo-type substrate is cleaved at the same position between Phe6 and Phe7. Accordingly, TPP Ⅰ shows two kinds of peptidase activities. One is a tripeptidyl peptidase activity and the other is a pepstatin insensitive carboxyl endopeptidase activity. Tripeptidyl peptidase activity and pepstatin insensitive carboxyl endopeptidase activity seem to be dual phases of one enzyme, TPP Ⅰ.

  11. Decreased T2 signal in the thalami may be a sign of lysosomal storage disease

    International Nuclear Information System (INIS)

    Lysosomal disorders are rare and are caused by genetically transmitted lysosomal enzyme deficiencies. A decreased T2 signal in the thalamus has occasionally been reported. Because the finding of bilateral abnormal signal intensity of the thalamus on T2-weighted images has not been systematically reviewed, and its value as a diagnostic tool critically evaluated, we carried out a systematic review of the literature. Articles in English with 30 trios of keywords were collected from PubMed. Exclusion criteria were lack of conventional T2-weighted images in the protocol and not being a human study. Finally, 111 articles were included. The thalamus was considered affected only if mentioned in the text or in the figure legends. Some 117 patients with various lysosomal diseases and five patients with ceruloplasmin deficiency were reported to have a bilateral decrease in T2 signal intensity. At least one article reported a bilateral decrease in signal intensity of the thalami on T2-weighted images in association with GM1 and GM2 gangliosidosis and with Krabbe's disease, aspartylglucosaminuria, mannosidosis, fucosidosis, and mucolipidosis IV. Furthermore, thalamic alteration was a consistent finding in several types of neuronal ceroid lipofuscinosis (NCL) including CLN1 (infantile NCL), CLN2 (classic late infantile NCL), CLN3 (juvenile NCL), CLN5 (Finnish variant late infantile NCL), and CLN7 (Turkish variant late infantile NCL). A decrease in T2 signal intensity in the thalami seems to be a sign of lysosomal disease. (orig.)

  12. Protein subcellular localization assays using split fluorescent proteins

    Science.gov (United States)

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2009-09-08

    The invention provides protein subcellular localization assays using split fluorescent protein systems. The assays are conducted in living cells, do not require fixation and washing steps inherent in existing immunostaining and related techniques, and permit rapid, non-invasive, direct visualization of protein localization in living cells. The split fluorescent protein systems used in the practice of the invention generally comprise two or more self-complementing fragments of a fluorescent protein, such as GFP, wherein one or more of the fragments correspond to one or more beta-strand microdomains and are used to "tag" proteins of interest, and a complementary "assay" fragment of the fluorescent protein. Either or both of the fragments may be functionalized with a subcellular targeting sequence enabling it to be expressed in or directed to a particular subcellular compartment (i.e., the nucleus).

  13. Competitive Protein Adsorption - Multilayer Adsorption and Surface Induced Protein Aggregation

    DEFF Research Database (Denmark)

    Holmberg, Maria; Hou, Xiaolin

    2009-01-01

    high concentration with investigation of single protein adsorption and interdependent adsorption between two specific proteins enables us to map protein adsorption sequences during competitive protein adsorption. Our study shows that proteins can adsorb in a multilayer fashion onto the polymer surfaces......In this study, competitive adsorption of albumin and IgG (immunoglobulin G) from human serum solutions and protein mixtures onto polymer surfaces is studied by means of radioactive labeling. By using two different radiolabels (125I and 131I), albumin and IgG adsorption to polymer surfaces is...... and that the outcome of IgG adsorption is much more sensitive to surface characteristics than the outcome of albumin adsorption. Using high concentrations of protein solution and hydrophobic polymer surfaces during adsorption can induce IgG aggregation, which is observed as extremely high Ig...

  14. Protein stress and stress proteins: implications in aging and disease

    Indian Academy of Sciences (India)

    C Sőti; Péter Csermely

    2007-04-01

    Environmantal stress induces damage that activates an adaptive response in any organism. The cellular stress response is based on the induction of cytoprotective proteins, the so called stress or heat shock proteins. The stress response as well as stress proteins are ubiquitous, highly conserved mechanism, and genes, respectively, already present in prokaryotes. Chaperones protect the proteome against conformational damage, promoting the function of protein networks. Protein damage takes place during aging and in several degenerative diseases, and presents a threat to overload the cellular defense mechanisms. The preservation of a robust stress response and protein disposal is indispensable for health and longevity. This review summarizes the present knowledge of protein damage, turnover, and the stress response in aging and degenerative diseases.

  15. Protein-protein interactions of mitochondrial-associated protein via bioluminescence resonance energy transfer

    Science.gov (United States)

    Koshiba, Takumi

    2015-01-01

    Protein-protein interactions are essential biological reactions occurring at inter- and intra-cellular levels. The analysis of their mechanism is generally required in order link to understand their various cellular functions. Bioluminescence resonance energy transfer (BRET), which is based on an enzymatic activity of luciferase, is a useful tool for investigating protein-protein interactions in live cells. The combination of the BRET system and biomolecular fluorescence complementation (BiFC) would provide us a better understanding of the hetero-oligomeric structural states of protein complexes. In this review, we discuss the application of BRET to the protein-protein interactions of mitochondrial-associated proteins and discuss its physiological relevance. PMID:27493852

  16. CPL:Detecting Protein Complexes by Propagating Labels on Protein-Protein Interaction Network

    Institute of Scientific and Technical Information of China (English)

    代启国; 郭茂祖; 刘晓燕; 滕志霞; 王春宇

    2014-01-01

    Proteins usually bind together to form complexes, which play an important role in cellular activities. Many graph clustering methods have been proposed to identify protein complexes by finding dense regions in protein-protein interaction networks. We present a novel framework (CPL) that detects protein complexes by propagating labels through interactions in a network, in which labels denote complex identifiers. With proper propagation in CPL, proteins in the same complex will be assigned with the same labels. CPL does not make any strong assumptions about the topological structures of the complexes, as in previous methods. The CPL algorithm is tested on several publicly available yeast protein-protein interaction networks and compared with several state-of-the-art methods. The results suggest that CPL performs better than the existing methods. An analysis of the functional homogeneity based on a gene ontology analysis shows that the detected complexes of CPL are highly biologically relevant.

  17. Discover Protein Complexes in Protein-Protein Interaction Networks Using Parametric Local Modularity

    OpenAIRE

    Tan Kai; Kim Jongkwang

    2010-01-01

    Abstract Background Recent advances in proteomic technologies have enabled us to create detailed protein-protein interaction maps in multiple species and in both normal and diseased cells. As the size of the interaction dataset increases, powerful computational methods are required in order to effectively distil network models from large-scale interactome data. Results We present an algorithm, miPALM (Module Inference by Parametric Local Modularity), to infer protein complexes in a protein-pr...

  18. HKC: An Algorithm to Predict Protein Complexes in Protein-Protein Interaction Networks

    OpenAIRE

    Xiaomin Wang; Zhengzhi Wang; Jun Ye

    2011-01-01

    With the availability of more and more genome-scale protein-protein interaction (PPI) networks, research interests gradually shift to Systematic Analysis on these large data sets. A key topic is to predict protein complexes in PPI networks by identifying clusters that are densely connected within themselves but sparsely connected with the rest of the network. In this paper, we present a new topology-based algorithm, HKC, to detect protein complexes in genome-scale PPI networks. HKC mainly use...

  19. Probabilistic methods for predicting protein functions in protein-protein interaction networks

    OpenAIRE

    Best, Christoph; Zimmer, Ralf; Apostolakis, Joannis

    2005-01-01

    We discuss probabilistic methods for predicting protein functions from protein-protein interaction networks. Previous work based on Markov Randon Fields is extended and compared to a general machine-learning theoretic approach. Using actual protein interaction networks for yeast from the MIPS database and GO-SLIM function assignments, we compare the predictions of the different probabilistic methods and of a standard support vector machine. It turns out that, with the currently available netw...

  20. Validation of protein carbonyl measurement

    DEFF Research Database (Denmark)

    Augustyniak, Edyta; Adam, Aisha; Wojdyla, Katarzyna; Rogowska-Wrzesinska, Adelina; Willetts, Rachel; Korkmaz, Ayhan; Atalay, Mustafa; Weber, Daniela; Grune, Tilman; Borsa, Claudia; Gradinaru, Daniela; Chand Bollineni, Ravi; Fedorova, Maria; Griffiths, Helen R

    Protein carbonyls are widely analysed as a measure of protein oxidation. Several different methods exist for their determination. A previous study had described orders of magnitude variance that existed when protein carbonyls were analysed in a single laboratory by ELISA using different commercial...... protein carbonyl analysis across Europe. ELISA and Western blotting techniques detected an increase in protein carbonyl formation between 0 and 5min of UV irradiation irrespective of method used. After irradiation for 15min, less oxidation was detected by half of the laboratories than after 5min...