The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Xiaowei Jiang - One of the best experts on this subject based on the ideXlab platform.
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protein Structural Disorder of the envelope v3 loop contributes to the switch in human immunodeficiency virus type 1 cell tropism
PLOS ONE, 2017Co-Authors: Xiaowei Jiang, Felix Feyertag, David L RobertsonAbstract:Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically Disordered (unstructured/Disordered) protein as it contains regions that do not fold into well-defined protein structures. These Disordered regions play important roles in HIV’s life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections. Why does this ‘rewiring’ event occur in HIV-1 infected patients? As changes in the charge of the V3 loop are associated with this receptor switch and it has been suggested that charged residues promote structure Disorder, we hypothesise that the intrinsic Disorder of the V3 loop is permissive to sequence variation thus contributing to the switch in cell tropism. To test this we use three independent data sets of gp120 to analyse V3 loop Disorder. We find that the V3 loop of X4 virus has significantly higher intrinsic Disorder tendency than R5 and R5X4 virus, while R5X4 virus has the lowest. These results indicate that Structural Disorder plays an important role in HIV-1 cell tropism and CXCR4 binding. We discuss the potential evolutionary mechanisms leading to the fixation of Disorder promoting mutations and the adaptive potential of protein Structural Disorder in viral host adaptation.
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protein Structural Disorder of the envelope v3 loop contributes to the switch in human immunodeficiency virus type 1 cell tropism
bioRxiv, 2017Co-Authors: Xiaowei Jiang, Felix Feyertag, David L RobertsonAbstract:Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically Disordered (unstructured/Disordered) protein as it contains regions that do not fold into well-defined protein structures. These Disordered regions play important roles in HIV9s life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections. Why does this ‘rewiring’ event occur in HIV-1 infected patients? As changes in the charge of the V3 loop are associated with this receptor switch and it has been suggested that charged residues promote structure Disorder, we hypothesise that the intrinsic Disorder of the V3 loop plays a role in determining cell tropism. To test this we use three independent data sets of gp120 to analyse V3 loop Disorder. We find that the V3 loop of X4 virus has significantly higher intrinsic Disorder tendency than R5 and R5X4 virus, while R5X4 virus has the lowest. These results indicate that Structural Disorder plays an important role in determining HIV-1 cell tropism and CXCR4 binding. We speculate that changes in N-linked glycosylation associated with tropism change (from R5 to X4) are required to stabilise the V3 loop with increased Disorder tendency during HIV-1 evolution. We discuss the potential evolutionary mechanisms leading to the fixation of Disorder promoting mutations and the adaptive potential of protein Structural Disorder in viral host adaptation.
David L Robertson - One of the best experts on this subject based on the ideXlab platform.
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protein Structural Disorder of the envelope v3 loop contributes to the switch in human immunodeficiency virus type 1 cell tropism
PLOS ONE, 2017Co-Authors: Xiaowei Jiang, Felix Feyertag, David L RobertsonAbstract:Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically Disordered (unstructured/Disordered) protein as it contains regions that do not fold into well-defined protein structures. These Disordered regions play important roles in HIV’s life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections. Why does this ‘rewiring’ event occur in HIV-1 infected patients? As changes in the charge of the V3 loop are associated with this receptor switch and it has been suggested that charged residues promote structure Disorder, we hypothesise that the intrinsic Disorder of the V3 loop is permissive to sequence variation thus contributing to the switch in cell tropism. To test this we use three independent data sets of gp120 to analyse V3 loop Disorder. We find that the V3 loop of X4 virus has significantly higher intrinsic Disorder tendency than R5 and R5X4 virus, while R5X4 virus has the lowest. These results indicate that Structural Disorder plays an important role in HIV-1 cell tropism and CXCR4 binding. We discuss the potential evolutionary mechanisms leading to the fixation of Disorder promoting mutations and the adaptive potential of protein Structural Disorder in viral host adaptation.
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protein Structural Disorder of the envelope v3 loop contributes to the switch in human immunodeficiency virus type 1 cell tropism
bioRxiv, 2017Co-Authors: Xiaowei Jiang, Felix Feyertag, David L RobertsonAbstract:Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically Disordered (unstructured/Disordered) protein as it contains regions that do not fold into well-defined protein structures. These Disordered regions play important roles in HIV9s life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections. Why does this ‘rewiring’ event occur in HIV-1 infected patients? As changes in the charge of the V3 loop are associated with this receptor switch and it has been suggested that charged residues promote structure Disorder, we hypothesise that the intrinsic Disorder of the V3 loop plays a role in determining cell tropism. To test this we use three independent data sets of gp120 to analyse V3 loop Disorder. We find that the V3 loop of X4 virus has significantly higher intrinsic Disorder tendency than R5 and R5X4 virus, while R5X4 virus has the lowest. These results indicate that Structural Disorder plays an important role in determining HIV-1 cell tropism and CXCR4 binding. We speculate that changes in N-linked glycosylation associated with tropism change (from R5 to X4) are required to stabilise the V3 loop with increased Disorder tendency during HIV-1 evolution. We discuss the potential evolutionary mechanisms leading to the fixation of Disorder promoting mutations and the adaptive potential of protein Structural Disorder in viral host adaptation.
Peter Tompa - One of the best experts on this subject based on the ideXlab platform.
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Essential functions linked with Structural Disorder in organisms of minimal genome
Biology Direct, 2016Co-Authors: Rita Pancsa, Peter TompaAbstract:Intrinsically Disordered regions (IDRs) of proteins fulfill important regulatory roles in most organisms. However, the proteins of certain endosymbiont and intracellular pathogenic bacteria with extremely reduced genomes contain disproportionately small amounts of IDRs, consisting almost entirely of folded domains. As their genomes co-evolving with their hosts have been reduced in unrelated lineages, the proteomes of these bacteria represent independently evolved minimal protein sets. We systematically analyzed Structural Disorder in a representative set of such minimal organisms to see which types of functionally relevant longer IDRs are invariably retained in them. We found that a few characteristic functions are consistently linked with conformational Disorder: ribosomal proteins, key components of the protein production machinery, a central coordinator of DNA metabolism and certain housekeeping chaperones seem to strictly rely on Structural Disorder even in genome-reduced organisms. We propose that these functions correspond to the most essential and probably also the most ancient ones fulfilled by Structural Disorder in cellular organisms. This article was reviewed by Michael Gromiha, Zoltan Gaspari and Sandor Pongor.
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SnapShot: Intrinsic Structural Disorder
Cell, 2015Co-Authors: Mainak Guharoy, Kris Pauwels, Peter TompaAbstract:Many proteins (intrinsically Disordered proteins, IDPs) or regions of proteins (intrinsically Disordered regions, IDRs) lack a well-defined 3D structure under physiological conditions. Albeit unfolded and highly dynamic, these proteins are not denatured; rather, intrinsic Structural Disorder is their native, functional state.
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Structural Disorder Provides Increased Adaptability for Vesicle Trafficking Pathways
PLOS Computational Biology, 2013Co-Authors: Natalia Pietrosemoli, Rita Pancsa, Peter TompaAbstract:Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles, while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main routes for human and yeast and analyzed them from the Structural Disorder perspective. We found similar overall Disorder content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups contain highly Disordered proteins, supporting the general importance of Structural Disorder in these routes, although some of them seem to heavily rely on Disorder, while others do not. Interestingly, the clathrin system is significantly more Disordered (~23%) than the other two, COPI (~9%) and COPII (~8%). We show that this Structural phenomenon enhances the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its prevalence in vesicle trafficking proteins and correlated it with Structural Disorder. Clathrin adaptors have the highest capability for moonlighting while also comprising the most highly Disordered members. The ability to acquire tissue specific functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for protein segments enriched in Structural Disorder and interaction sites. Overall, our results confirm the general importance of Structural Disorder in vesicle trafficking and suggest major roles for this Structural property in shaping the differences of evolutionary adaptability in the three routes.
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Exon-phase symmetry and intrinsic Structural Disorder promote modular evolution in the human genome
Nucleic Acids Research, 2013Co-Authors: Eva Schad, Lajos Kalmár, Peter TompaAbstract:A key signature of module exchange in the genome is phase symmetry of exons, suggestive of exon shuffling events that occurred without disrupting translation reading frame. At the protein level, intrinsic Structural Disorder may be another key element because Disordered regions often serve as functional elements that can be effectively integrated into a protein structure. Therefore, we asked whether exon-phase symmetry in the human genome and Structural Disorder in the human proteome are connected, signalling such evolutionary mechanisms in the assembly of multi-exon genes. We found an elevated level of Structural Disorder of regions encoded by symmetric exons and a preferred symmetry of exons encoding for mostly Disordered regions (>70% predicted Disorder). Alternatively spliced symmetric exons tend to correspond to the most Disordered regions. The genes of mostly Disordered proteins (>70% predicted Disorder) tend to be assembled from symmetric exons, which often arise by internal tandem duplications. Preponderance of certain types of short motifs (e.g. SH3-binding motif) and domains (e.g. high-mobility group domains) suggests that certain Disordered modules have been particularly effective in exonshuffling events. Our observations suggest that Structural Disorder has facilitated modular assembly of complex genes in evolution of the human genome.
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Structural Disorder in eukaryotes
PLOS ONE, 2012Co-Authors: Rita Pancsa, Peter TompaAbstract:Based on early bioinformatic studies on a handful of species, the frequency of Structural Disorder of proteins is generally thought to be much higher in eukaryotes than in prokaryotes. To refine this view, we present here a comparative prediction study and analysis of 194 fully described eukaryotic proteomes and 87 reference prokaryotes for Structural Disorder. We found that Structural Disorder does distinguish eukaryotes from prokaryotes, but its frequency spans a very wide range in the two superkingdoms that largely overlap. The number of Disordered binding regions and different Pfam domain types also contribute to distinguish eukaryotes from prokaryotes. Unexpectedly, the highest levels – and highest variability – of predicted Disorder is found in protists, i.e. single-celled eukaryotes, often surpassing more complex eukaryote organisms, plants and animals. This trend contrasts with that of the number of domain types, which increases rather monotonously toward more complex organisms. The level of Structural Disorder appears to be strongly correlated with lifestyle, because some obligate intracellular parasites and endosymbionts have the lowest levels, whereas host-changing parasites have the highest level of predicted Disorder. We conclude that protists have been the evolutionary hot-bed of experimentation with Structural Disorder, in a period when Structural Disorder was actively invented and the major functional classes of Disordered proteins established.
Felix Feyertag - One of the best experts on this subject based on the ideXlab platform.
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protein Structural Disorder of the envelope v3 loop contributes to the switch in human immunodeficiency virus type 1 cell tropism
PLOS ONE, 2017Co-Authors: Xiaowei Jiang, Felix Feyertag, David L RobertsonAbstract:Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically Disordered (unstructured/Disordered) protein as it contains regions that do not fold into well-defined protein structures. These Disordered regions play important roles in HIV’s life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections. Why does this ‘rewiring’ event occur in HIV-1 infected patients? As changes in the charge of the V3 loop are associated with this receptor switch and it has been suggested that charged residues promote structure Disorder, we hypothesise that the intrinsic Disorder of the V3 loop is permissive to sequence variation thus contributing to the switch in cell tropism. To test this we use three independent data sets of gp120 to analyse V3 loop Disorder. We find that the V3 loop of X4 virus has significantly higher intrinsic Disorder tendency than R5 and R5X4 virus, while R5X4 virus has the lowest. These results indicate that Structural Disorder plays an important role in HIV-1 cell tropism and CXCR4 binding. We discuss the potential evolutionary mechanisms leading to the fixation of Disorder promoting mutations and the adaptive potential of protein Structural Disorder in viral host adaptation.
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protein Structural Disorder of the envelope v3 loop contributes to the switch in human immunodeficiency virus type 1 cell tropism
bioRxiv, 2017Co-Authors: Xiaowei Jiang, Felix Feyertag, David L RobertsonAbstract:Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically Disordered (unstructured/Disordered) protein as it contains regions that do not fold into well-defined protein structures. These Disordered regions play important roles in HIV9s life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections. Why does this ‘rewiring’ event occur in HIV-1 infected patients? As changes in the charge of the V3 loop are associated with this receptor switch and it has been suggested that charged residues promote structure Disorder, we hypothesise that the intrinsic Disorder of the V3 loop plays a role in determining cell tropism. To test this we use three independent data sets of gp120 to analyse V3 loop Disorder. We find that the V3 loop of X4 virus has significantly higher intrinsic Disorder tendency than R5 and R5X4 virus, while R5X4 virus has the lowest. These results indicate that Structural Disorder plays an important role in determining HIV-1 cell tropism and CXCR4 binding. We speculate that changes in N-linked glycosylation associated with tropism change (from R5 to X4) are required to stabilise the V3 loop with increased Disorder tendency during HIV-1 evolution. We discuss the potential evolutionary mechanisms leading to the fixation of Disorder promoting mutations and the adaptive potential of protein Structural Disorder in viral host adaptation.
F. Franco - One of the best experts on this subject based on the ideXlab platform.
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the effect of ultrasound on the particle size and Structural Disorder of a well ordered kaolinite
Journal of Colloid and Interface Science, 2004Co-Authors: F. Franco, Luis A Perezmaqueda, J L PerezrodriguezAbstract:Abstract The present study examined the effect of sonication on the particle size and structure of a well-crystallized (KGa-1) kaolinite from Georgia. Sonication produced an important delamination effect as well as a reduction of the other particle-size dimensions. The experiments, carried out under different experimental conditions, showed that particle-size reduction can be controlled through different variables such as power of ultrasonic processor, amount of sample (kaolinite + water), and time of treatment. As a consequence of this particle-size reduction the surface area increases sharply with the sonication time from 8.5 to 83 m2/g after 20 h with the most energetic treatment. Contrary to what is observed in the grinding treatment, sonication did not cause the amorphization of kaolinite, as observed by XRD and FTIR data. Nevertheless, ultrasound treatment increased the Structural Disorder, which consisted in increases in the proportion of specific translations (−a/3+b/3) between adjacent layers in the first hours of treatment, followed by increases in the proportion of random translations between layers.
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The effect of ultrasound on the particle size and Structural Disorder of a well-ordered kaolinite
Journal of Colloid and Interface Science, 2004Co-Authors: F. Franco, L. A. Perez-maqueda, José Luis Perez-rodriguezAbstract:The present study examined the effect of sonication on the particle size and structure of a well-crystallized (KGa-1) kaolinite from Georgia. Sonication produced an important delamination effect as well as a reduction of the other particle-size dimensions. The experiments, carried out under different experimental conditions, showed that particle-size reduction can be controlled through different variables such as power of ultrasonic processor, amount of sample (kaolinite + water), and time of treatment. As a consequence of this particle-size reduction the surface area increases sharply with the sonication time from 8.5 to 83 m2/g after 20 h with the most energetic treatment. Contrary to what is observed in the grinding treatment, sonication did not cause the amorphization of kaolinite, as observed by XRD and FTIR data. Nevertheless, ultrasound treatment increased the Structural Disorder, which consisted in increases in the proportion of specific translations (-a/3+b/3) between adjacent layers in the first hours of treatment, followed by increases in the proportion of random translations between layers. © 2003 Elsevier Inc. All rights reserved.
