The Experts below are selected from a list of 4905 Experts worldwide ranked by ideXlab platform
David R Westhead - One of the best experts on this subject based on the ideXlab platform.
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TMB-Hunt: a web server to screen sequence sets for transmembrane Beta-Barrel proteins.
Nucleic acids research, 2005Co-Authors: Andrew G Garrow, Alison Agnew, David R WestheadAbstract:TMB-Hunt is a program that uses a modified k-nearest neighbour (k-NN) algorithm to classify protein sequences as transmembrane Beta-Barrel (TMB) or non-TMB on the basis of whole sequence amino acid composition. By including differentially weighted amino acids, evolutionary information and by calibrating the scoring, a discrimination accuracy of 92.5% was achieved, as tested using a rigorous cross-validation procedure. The TMB-Hunt web server, available at www.bioinformatics.leeds.ac.uk/BetaBarrel, allows screening of up to 10,000 sequences in a single query and provides results and key statistics in a simple colour coded format.
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TMB-Hunt: An amino acid composition based method to screen proteomes for Beta-Barrel transmembrane proteins
BMC bioinformatics, 2005Co-Authors: Andrew G Garrow, Alison Agnew, David R WestheadAbstract:Background Beta-Barrel transmembrane (bbtm) proteins are a functionally important and diverse group of proteins expressed in the outer membranes of bacteria (both gram negative and acid fast gram positive), mitochondria and chloroplasts. Despite recent publications describing reasonable levels of accuracy for discriminating between bbtm proteins and other proteins, screening of entire genomes remains troublesome as these molecules only constitute a small fraction of the sequences screened. Therefore, novel methods are still required capable of detecting new families of bbtm protein in diverse genomes.
Ludvig M. Sollid - One of the best experts on this subject based on the ideXlab platform.
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Transglutaminase 2 strongly binds to an extracellular matrix component other than fibronectin via its second C‐terminal Beta‐Barrel domain
The FEBS journal, 2016Co-Authors: Jorunn Stamnaes, Inês Cardoso, Rasmus Iversen, Ludvig M. SollidAbstract:Transglutaminase 2 (TG2) is a ubiquitous cross-linking enzyme present both intra- and extracellular in many cell types and tissues. TG2 is upregulated upon cellular stress or injury, and extracellular TG2 is implicated in several human diseases, including celiac disease. However, incomplete knowledge about extracellular TG2 biology limits our understanding of how TG2 is involved in disease. Here, we demonstrate that binding of TG2 to the ECM of small intestinal tissue sections is the sum of binding to fibronectin (FN) via its N-terminal domain and binding to an abundant, novel ECM interaction partner via its second C-terminal Beta-Barrel domain. The latter interaction dominates and gives rise to the characteristic reticular staining pattern of extracellular TG2. Of relevance for celiac disease, we show that self-multimerized TG2 does not efficiently deposit in intestinal ECM, and TG2 complexes may thus become free-floating antigens in tissues in contrast to monomeric TG2 that would readily become sequestered by the ECM. Upon injection of monoclonal antibody targeting the FN binding site, we observe antibody deposition on extracellular TG2 in cryosections, suggesting that the FN binding site of TG2 is exposed in vivo. This would explain how and why celiac autoantibodies recognizing the FN binding site of TG2 can bind TG2 in vitro, in situ as well as in vivo This article is protected by copyright. All rights reserved.
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transglutaminase 2 strongly binds to an extracellular matrix component other than fibronectin via its second c terminal Beta Barrel domain
FEBS Journal, 2016Co-Authors: Jorunn Stamnaes, Inês Cardoso, Rasmus Iversen, Ludvig M. SollidAbstract:Transglutaminase 2 (TG2) is a ubiquitous cross-linking enzyme present both intra- and extracellular in many cell types and tissues. TG2 is upregulated upon cellular stress or injury, and extracellular TG2 is implicated in several human diseases, including celiac disease. However, incomplete knowledge about extracellular TG2 biology limits our understanding of how TG2 is involved in disease. Here, we demonstrate that binding of TG2 to the ECM of small intestinal tissue sections is the sum of binding to fibronectin (FN) via its N-terminal domain and binding to an abundant, novel ECM interaction partner via its second C-terminal Beta-Barrel domain. The latter interaction dominates and gives rise to the characteristic reticular staining pattern of extracellular TG2. Of relevance for celiac disease, we show that self-multimerized TG2 does not efficiently deposit in intestinal ECM, and TG2 complexes may thus become free-floating antigens in tissues in contrast to monomeric TG2 that would readily become sequestered by the ECM. Upon injection of monoclonal antibody targeting the FN binding site, we observe antibody deposition on extracellular TG2 in cryosections, suggesting that the FN binding site of TG2 is exposed in vivo. This would explain how and why celiac autoantibodies recognizing the FN binding site of TG2 can bind TG2 in vitro, in situ as well as in vivo This article is protected by copyright. All rights reserved.
David M. Mueller - One of the best experts on this subject based on the ideXlab platform.
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Structure/function of the Beta-Barrel domain of F1-ATPase in the yeast Saccharomyces cerevisiae.
The Journal of biological chemistry, 1999Co-Authors: Niki Bakhtiari, Jie Lai-zhang, Bingyi Yao, David M. MuellerAbstract:The first 90 amino acids of the alpha- and Beta-subunits of mitochondrial F1-ATPase are folded into Beta-Barrel domains and were postulated to be important for stabilizing the enzyme (Abrahams, J. P., Leslie, A. G., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628). The role of the domains was studied by making chimeric enzymes, replacing the domains from the yeast Saccharomyces cerevisiae enzyme with the corresponding domains from the enzyme of the thermophilic bacterium Bacillus PS3. The enzymes containing the chimeric alpha-, Beta-, or alpha- and Beta-subunits were not functional. However, gain-of-function mutations were obtained from the strain containing the enzyme with the chimeric PS3/yeast Beta-subunit. The gain-of-function mutations were all in codons encoding the Beta-Barrel domain of the Beta-subunit, and the residues appear to map out a region of subunit-subunit interactions. Gain-of-function mutations were also obtained that provided functional expression of the chimeric PS3/yeast alpha- and Beta-subunits together. Biochemical analysis of this active chimeric enzyme indicated that it was not significantly more thermostable or labile than the wild type. The results of this study indicate that the Beta-Barrel domains form critical contacts (distinct from those between the alpha- and Beta-subunits) that are important for the assembly of the ATP synthase.
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structure function of the Beta Barrel domain of f1 atpase in the yeast saccharomyces cerevisiae
Journal of Biological Chemistry, 1999Co-Authors: Niki Bakhtiari, Bingyi Yao, Jie Laizhang, David M. MuellerAbstract:The first 90 amino acids of the alpha- and Beta-subunits of mitochondrial F1-ATPase are folded into Beta-Barrel domains and were postulated to be important for stabilizing the enzyme (Abrahams, J. P., Leslie, A. G., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628). The role of the domains was studied by making chimeric enzymes, replacing the domains from the yeast Saccharomyces cerevisiae enzyme with the corresponding domains from the enzyme of the thermophilic bacterium Bacillus PS3. The enzymes containing the chimeric alpha-, Beta-, or alpha- and Beta-subunits were not functional. However, gain-of-function mutations were obtained from the strain containing the enzyme with the chimeric PS3/yeast Beta-subunit. The gain-of-function mutations were all in codons encoding the Beta-Barrel domain of the Beta-subunit, and the residues appear to map out a region of subunit-subunit interactions. Gain-of-function mutations were also obtained that provided functional expression of the chimeric PS3/yeast alpha- and Beta-subunits together. Biochemical analysis of this active chimeric enzyme indicated that it was not significantly more thermostable or labile than the wild type. The results of this study indicate that the Beta-Barrel domains form critical contacts (distinct from those between the alpha- and Beta-subunits) that are important for the assembly of the ATP synthase.
Dennis H. Bamford - One of the best experts on this subject based on the ideXlab platform.
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Virus evolution: how far does the double |[Beta]|-Barrel viral lineage extend?
Nature reviews. Microbiology, 2008Co-Authors: Mart Krupovic, Dennis H. BamfordAbstract:During the past few years one of the most astonishing findings in the field of virology has been the realization that viruses that infect hosts from all three domains of life are often structurally similar. The recent burst of structural information points to a need to create a new way to organize the virosphere that, in addition to the current classification, would reflect relationships between virus families. Using the vertical Beta-Barrel major capsid proteins and ATPases related to known viral genome-packaging ATPases as examples, we can now re-evaluate the classification of viruses and virus-like genetic elements from a structural standpoint.
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Virus evolution: how far does the double Beta-Barrel viral lineage extend?
Nature Reviews Microbiology, 2008Co-Authors: Mart Krupovic, Dennis H. BamfordAbstract:During the past few years one of the most astonishing findings in the field of virology has been the realization that viruses that infect hosts from all three domains of life are often structurally similar. The recent burst of structural information points to a need to create a new way to organize the virosphere that, in addition to the current classification, would reflect relationships between virus families. Using the vertical Beta-Barrel major capsid proteins and ATPases related to known viral genome-packaging ATPases as examples, we can now re-evaluate the classification of viruses and virus-like genetic elements from a structural standpoint.
Kausik Chattopadhyay - One of the best experts on this subject based on the ideXlab platform.
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Revisiting the oligomerization mechanism of Vibrio cholerae cytolysin, a Beta-Barrel pore-forming toxin
Biochemical and biophysical research communications, 2016Co-Authors: Anand Kumar Rai, Kausik ChattopadhyayAbstract:Vibrio cholerae cytolysin (VCC) is a membrane-damaging Beta-Barrel pore-forming toxin (Beta-PFT). VCC causes permeabilization of the target membranes by forming transmembrane oligomeric Beta-Barrel pores. Oligomerization is a key step in the mode of action of any Beta-PFT, including that of VCC. Earlier studies have identified some of the key residues in VCC that are directly involved in the generation of the inter-protomer contacts, thus playing critical roles in the oligomerization of the membrane-bound toxin. Analysis of the VCC oligomeric pore structure reveals a potential hydrogen-bond network that appears to connect the sidechain of an asparagine residue (Asn582; located within an inter-domain linker sequence) from one protomer to the backbone CO- and NH-groups of the neighbouring protomer, indirectly through water molecules at most of the inter-protomer interfaces. In the present study, we show that the mutation of Asn582Ala affects the oligomerization and the pore-forming activity of VCC in the membrane lipid bilayer of the synthetic lipid vesicles, while the replacement of Asn582Gln results into the restoration of the oligomeric pore-forming ability of the toxin. Using a number of truncated variants of VCC, having deletion in the C-terminal region of the toxin starting from the Asn582 residue or beyond, we also show that the presence of Asn582 is critically required for the oligomerization of the truncated form of the protein.
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Physicochemical constraints of elevated pH affect efficient membrane interaction and arrest an abortive membrane-bound oligomeric intermediate of the Beta-Barrel pore-forming toxin Vibrio cholerae cytolysin.
Archives of biochemistry and biophysics, 2015Co-Authors: Anand Kumar Rai, Nidhi Kundu, Kausik ChattopadhyayAbstract:Vibrio cholerae cytolysin (VCC) is a potent membrane-damaging cytotoxic protein. VCC causes permeabilization of the target cell membranes by forming transmembrane oligomeric Beta-Barrel pores. Membrane pore formation by VCC involves following key steps: (i) membrane binding, (ii) formation of a pre-pore oligomeric intermediate, (iii) membrane insertion of the pore-forming motifs, and (iv) formation of the functional transmembrane pore. Membrane binding, oligomerization, and subsequent pore-formation process of VCC appear to be facilitated by multiple regulatory mechanisms that are only partly understood. Here, we have explored the role(s) of the physicochemical constraints, specifically imposed by the elevated pH conditions, on the membrane pore-formation mechanism of VCC. Elevated pH abrogates efficient interaction of VCC with the target membranes, and blocks its pore-forming activity. Under the elevated pH conditions, membrane-bound fractions of VCC remain trapped in the form of abortive oligomeric species that fail to generate the functional transmembrane pores. Such an abortive oligomeric assembly appears to represent a distinct, more advanced intermediate state than the pre-pore state. The present study offers critical insights regarding the implications of the physicochemical constraints for regulating the efficient membrane interaction and pore formation by VCC.