The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Vladimir N Uversky - One of the best experts on this subject based on the ideXlab platform.
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Viral Disorder or Disordered Viruses: Do Viral Proteins Possess Unique Features?
Protein and Peptide Letters, 2010Co-Authors: Robert W. Williams, Christopher J. Oldfield, A. Keith Dunker, Vladimir N UverskyAbstract:Many Proteins or their regions are disordered in their native, biologically active states. Bioinformatics has revealed that these Proteins/regions are highly abundant in different proteomes and carry out mostly regulatory functions related to molecular recognition, signal transduction, protein-protein, and protein-nucleic acid interactions. Viruses, these “organisms at the edge of life”, have uniquely evolved to be highly adaptive for fast change in their biological and physical environment. To sustain these fast environmental changes, Viral Proteins elaborated multiple measures, from relatively low van der Waals contact densities, to inclusion of a large fraction of residues that are not arranged in well-defined secondary structural elements, to heavy use of short disordered regions, and to high resistance to mutations. On the other hand, Viral Proteins are rich in intrinsic disorder. Some of the intrinsically disordered regions are heavily used in the functioning of Viral Proteins. Others likely have evolved to help viruses accommodate to their hostile habitats. Still others evolved to help viruses in managing their economic usage of genetic material via alternative splicing, overlapping genes, and anti-sense transcription. In this review, we focus on structural peculiarities of Viral Proteins and on the role of intrinsic disorder in their functions.
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Intrinsic disorder in Viral Proteins Genome-Linked: experimental and predictive analyses
Virology Journal, 2009Co-Authors: Eugénie Hébrard, Vladimir N Uversky, Sonia Longhi, Yannick Bessin, Thierry Michon, François Delalande, Alain Van Dorsselaer, Pedro Romero, Jocelyne Walter, Nathalie DeclerckAbstract:Background VPgs are Viral Proteins linked to the 5' end of some Viral genomes. Interactions between several VPgs and eukaryotic translation initiation factors eIF4Es are critical for plant infection. However, VPgs are not restricted to phytoviruses, being also involved in genome replication and protein translation of several animal viruses. To date, structural data are still limited to small picornaViral VPgs. Recently three phytoViral VPgs were shown to be natively unfolded Proteins. Results In this paper, we report the bacterial expression, purification and biochemical characterization of two phytoViral VPgs, namely the VPgs of Rice yellow mottle virus (RYMV, genus Sobemovirus ) and Lettuce mosaic virus (LMV, genus Potyvirus ). Using far-UV circular dichroism and size exclusion chromatography, we show that RYMV and LMV VPgs are predominantly or partly unstructured in solution, respectively. Using several disorder predictors, we show that both Proteins are predicted to possess disordered regions. We next extend theses results to 14 VPgs representative of the Viral diversity. Disordered regions were predicted in all VPg sequences whatever the genus and the family. Conclusion Based on these results, we propose that intrinsic disorder is a common feature of VPgs. The functional role of intrinsic disorder is discussed in light of the biological roles of VPgs.
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Do Viral Proteins possess unique biophysical features
Trends in Biochemical Sciences, 2008Co-Authors: Nobuhiko Tokuriki, Vladimir N Uversky, Christopher J. Oldfield, Igor N. Berezovsky, Dan S. TawfikAbstract:Natural selection shapes the sequence, structure and biophysical properties of Proteins to fit their environment. We hypothesize that highly thermostable Proteins and Viral Proteins represent two opposing adaptation strategies. Thermostable Proteins are highly compact and possess well-packed hydrophobic cores and intensely charged surfaces. By contrast, Viral Proteins, and RNA Viral Proteins in particular, display a high occurrence of disordered segments and loosely packed cores. These features might endow Viral Proteins with increased structural flexibility and effective ways to interact with the components of the host. They could also be related to high adaptability levels and mutation rates observed in viruses, thus, representing a unique strategy for buffering the deleterious effects of mutations, such that those that have little (interactions), have little to lose.
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Protein intrinsic disorder toolbox for comparative analysis of Viral Proteins
BMC Genomics, 2008Co-Authors: A. Keith Dunker, Vladimir N UverskyAbstract:To examine the usefulness of protein disorder predictions as a tool for the comparative analysis of Viral Proteins, a relational database has been constructed. The database includes Proteins from influenza A and HIV-related viruses. Annotations include Viral protein sequence, disorder prediction, structure, and function. Location of each protein within a virion, if known, is also denoted. Our analysis reveals a clear relationship between proximity to the RNA core and the percentage of predicted disordered residues for a set of influenza A virus Proteins.
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Protein intrinsic disorder toolbox for comparative analysis of Viral Proteins.
BMC genomics, 2008Co-Authors: A. Keith Dunker, Vladimir N UverskyAbstract:To examine the usefulness of protein disorder predictions as a tool for the comparative analysis of Viral Proteins, a relational database has been constructed. The database includes Proteins from influenza A and HIV-related viruses. Annotations include Viral protein sequence, disorder prediction, structure, and function. Location of each protein within a virion, if known, is also denoted. Our analysis reveals a clear relationship between proximity to the RNA core and the percentage of predicted disordered residues for a set of influenza A virus Proteins. Neuraminidases (NA) and hemagglutinin (HA) of major influenza A pandemics tend to pair in such a way that both Proteins tend to be either ordered-ordered or disordered-disordered by prediction. This may be the result of these Proteins evolving from being lipid-associated. High abundance of intrinsic disorder in envelope and matrix Proteins from HIV-related viruses likely represents a mechanism where HIV virions can escape immune response despite the availability of antibodies for the HIV-related Proteins. This exercise provides an example showing how the combined use of intrinsic disorder predictions and relational databases provides an improved understanding of the functional and structural behaviour of Viral Proteins.
Genhong Cheng - One of the best experts on this subject based on the ideXlab platform.
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parp12 suppresses zika virus infection through parp dependent degradation of ns1 and ns3 Viral Proteins
Science Signaling, 2018Co-Authors: Hui Zhao, Ping Liu, Natalie Quanquin, Nina Sun, Chengfeng Qin, Genhong ChengAbstract:Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses Viral replication. Type I IFNs exert antiViral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiViral ISGs that restricted Zika virus replication, we individually knocked out 21 ISGs in A549 lung cancer cells and identified PARP12 as a strong inhibitor of Zika virus replication. Our findings suggest that PARP12 mediated the ADP-ribosylation of NS1 and NS3, nonstructural Viral Proteins that are involved in Viral replication and modulating host defense responses. This modification of NS1 and NS3 triggered their proteasome-mediated degradation. These data increase our understanding of the antiViral activity of PARP12 and suggest a molecular basis for the potential development of therapeutics against Zika virus.
Mt Hallett - One of the best experts on this subject based on the ideXlab platform.
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Predicting the subcellular localization of Viral Proteins within a mammalian host cell
Virology journal, 2006Co-Authors: Scott, R Oomen, Dy Thomas, Mt HallettAbstract:The bioinformatic prediction of protein subcellular localization has been extensively studied for prokaryotic and eukaryotic organisms. However, this is not the case for viruses whose Proteins are often involved in extensive interactions at various subcellular localizations with host Proteins. Here, we investigate the extent of utilization of human cellular localization mechanisms by Viral Proteins and we demonstrate that appropriate eukaryotic subcellular localization predictors can be used to predict Viral protein localization within the host cell. Such predictions provide a method to rapidly annotate Viral proteomes with subcellular localization information. They are likely to have widespread applications both in the study of the functions of Viral Proteins in the host cell and in the design of antiViral drugs.
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Predicting the subcellular localization of Viral Proteins within a mammalian host cell
Virology Journal, 2006Co-Authors: Ms Scott, R Oomen, Dy Thomas, Mt HallettAbstract:Background The bioinformatic prediction of protein subcellular localization has been extensively studied for prokaryotic and eukaryotic organisms. However, this is not the case for viruses whose Proteins are often involved in extensive interactions at various subcellular localizations with host Proteins. Results Here, we investigate the extent of utilization of human cellular localization mechanisms by Viral Proteins and we demonstrate that appropriate eukaryotic subcellular localization predictors can be used to predict Viral protein localization within the host cell. Conclusion Such predictions provide a method to rapidly annotate Viral proteomes with subcellular localization information. They are likely to have widespread applications both in the study of the functions of Viral Proteins in the host cell and in the design of antiViral drugs.
Dan S. Tawfik - One of the best experts on this subject based on the ideXlab platform.
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Do Viral Proteins possess unique biophysical features
Trends in Biochemical Sciences, 2008Co-Authors: Nobuhiko Tokuriki, Vladimir N Uversky, Christopher J. Oldfield, Igor N. Berezovsky, Dan S. TawfikAbstract:Natural selection shapes the sequence, structure and biophysical properties of Proteins to fit their environment. We hypothesize that highly thermostable Proteins and Viral Proteins represent two opposing adaptation strategies. Thermostable Proteins are highly compact and possess well-packed hydrophobic cores and intensely charged surfaces. By contrast, Viral Proteins, and RNA Viral Proteins in particular, display a high occurrence of disordered segments and loosely packed cores. These features might endow Viral Proteins with increased structural flexibility and effective ways to interact with the components of the host. They could also be related to high adaptability levels and mutation rates observed in viruses, thus, representing a unique strategy for buffering the deleterious effects of mutations, such that those that have little (interactions), have little to lose.
Dmitri S Kudryashov - One of the best experts on this subject based on the ideXlab platform.
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Thermodynamic instability of Viral Proteins is a pathogen-associated molecular pattern targeted by human defensins
Scientific Reports, 2016Co-Authors: Elena Kudryashova, Pratibha C. Koneru, Adam A. Strömstedt, Mamuka Kvaratskhelia, Wuyuan Lu, Dmitri S KudryashovAbstract:Human defensins are innate immune defense peptides with a remarkably broad repertoire of anti-pathogen activities. In addition to modulating immune response, inflammation and angiogenesis, disintegrating bacterial membranes and inactivating bacterial toxins, defensins are known to intercept various viruses at different stages of their life cycles, while remaining relatively benign towards human cells and Proteins. Recently we have found that human defensins inactivate proteinaceous bacterial toxins by taking advantage of their low thermodynamic stability and acting as natural “anti-chaperones”, i.e. destabilizing the native conformation of the toxins. In the present study we tested various Proteins produced by several viruses (HIV-1, PFV and TEV) and found them to be susceptible to destabilizing effects of human α-defensins HNP-1 and HD-5 and the synthetic θ-defensin RC-101, but not β-defensins hBD-1 and hBD-2 or structurally related plant-derived peptides. Defensin-induced unfolding promoted exposure of hydrophobic groups otherwise confined to the core of the Viral Proteins. This resulted in precipitation, an enhanced susceptibility to proteolytic cleavage and a loss of Viral protein activities. We propose, that defensins recognize and target a common and essential physico-chemical property shared by many bacterial toxins and Viral Proteins – the intrinsically low thermodynamic protein stability.
