ArticleThe Journal of biological chemistry2011
Domain 3 of NS5A protein from the hepatitis C virus has intrinsic alpha-helical propensity and is a substrate of cyclophilin A.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 100 citations in OpenAlex.
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Mutational analysis reveals a novel role for hepatitis C virus NS5A domain I in cyclophilin-dependent genome replication.The Journal of general virology · 2023Article
- Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.Viruses · 2023Article
- Viral RNA Is a Hub for Critical Host-Virus Interactions.Sub-cellular biochemistry · 2023Article
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022Review
- Regulatory Role of Phospholipids in Hepatitis C Virus Replication and Protein Function.Pathogens (Basel, Switzerland) · 2022Review
- Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes.International journal of molecular sciences · 2022Article
- MxB Disrupts Hepatitis C Virus NS5A-CypA Complex: Insights From a Combined Theoretical and Experimental Approach.Frontiers in microbiology · 2022Article
- Role of "dual-personality" fragments in HEV adaptation-analysis of Y-domain region.Journal, genetic engineering & biotechnology · 2021Article
- Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches.Pathogens (Basel, Switzerland) · 2021Review
- Dimer Organization of Membrane-Associated NS5A of Hepatitis C Virus as Determined by Highly SensitiveAngewandte Chemie (International ed. in English) · 2021Article
- ISGylation of Hepatitis C Virus NS5A Protein Promotes Viral RNA Replication via Recruitment of Cyclophilin A.Journal of virology · 2020Article
- Proteostasis in Viral Infection: Unfolding the Complex Virus-Chaperone Interplay.Cold Spring Harbor perspectives in biology · 2020Review
- Intrinsically disordered proteins of viruses: Involvement in the mechanism of cell regulation and pathogenesis.Progress in molecular biology and translational science · 2020Review
- Cyclophilin A allows the allosteric regulation of a structural motif in the disordered domain 2 of NS5A and thereby fine-tunes HCV RNA replication.The Journal of biological chemistry · 2019Article
- Symmetric Anti-HCV Agents: Synthesis, Antiviral Properties, and Conformational Aspects of Core Scaffolds.ACS omega · 2019Article
- Differences across cyclophilin A orthologs contribute to the host range restriction of hepatitis C virus.eLife · 2019Article
- Human MxB Inhibits the Replication of Hepatitis C Virus.Journal of virology · 2019Article
- Characterization of a Threonine-Rich Cluster in Hepatitis C Virus Nonstructural Protein 5A and Its Contribution to Hyperphosphorylation.Journal of virology · 2018Article
- Intracellular Hepatitis C Virus Modeling Predicts Infection Dynamics and Viral Protein Mechanisms.Journal of virology · 2018Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonstructural protein 5A (NS5A) is essential for hepatitis C virus (HCV) replication and constitutes an attractive target for antiviral drug development. Although structural data for its in-plane membrane anchor and domain D1 are available, the structure of domains 2 (D2) and 3 (D3) remain poorly defined. We report here a comparative molecular characterization of the NS5A-D3 domains of the HCV JFH-1 (genotype 2a) and Con1 (genotype 1b) strains. Combining gel filtration, CD, and NMR spectroscopy analyses, we show that NS5A-D3 is natively unfolded. However, NS5A-D3 domains from both JFH-1 and Con1 strains exhibit a propensity to partially fold into an α-helix. NMR analysis identifies two putative α-helices, for which a molecular model could be obtained. The amphipathic nature of the first helix and its conservation in all genotypes suggest that it might correspond to a molecular recognition element and, as such, promote the interaction with relevant biological partner(s). Because mutations conferring resistance to cyclophilin inhibitors have been mapped into NS5A-D3, we also investigated the functional interaction between NS5A-D3 and cyclophilin A (CypA). CypA indeed interacts with NS5A-D3, and this interaction is completely abolished by cyclosporin A. NMR heteronuclear exchange experiments demonstrate that CypA has in vitro peptidyl-prolyl cis/trans-isomerase activity toward some, but not all, of the peptidyl-prolyl bonds in NS5A-D3. These studies lead to novel insights into the structural features of NS5A-D3 and its relationships with CypA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.