ArticleThe Journal of biological chemistry2009
Hepatitis C virus NS5A protein is a substrate for the peptidyl-prolyl cis/trans isomerase activity of cyclophilins A and B.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 162 citations in OpenAlex.
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Cyclophilin A: promising target in cancer therapy.Cancer biology & therapy · 2024Review
- Article
- Detection of Hepatitis C Virus Infection from Patient Sera in Cell Culture Using Semi-Automated Image Analysis.Viruses · 2024Article
- Functional Role of Hepatitis C Virus NS5A in the Regulation of Autophagy.Pathogens (Basel, Switzerland) · 2024Review
- Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes.Journal of virology · 2024Article
- Picosecond Dynamics of a Small Molecule in Its Bound State with an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2024Article
- Mutational analysis reveals a novel role for hepatitis C virus NS5A domain I in cyclophilin-dependent genome replication.The Journal of general virology · 2023Article
- PIN1 and PIN4 inhibitionFrontiers in microbiology · 2023Article
- Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 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
- Emerging Roles of Cyclophilin A in Regulating Viral Cloaking.Frontiers in microbiology · 2022Review
- The Inherent Dynamics and Interaction Sites of the SARS-CoV-2 Nucleocapsid N-Terminal Region.Journal of molecular biology · 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
- The Role of Cyclophilins in Inflammatory Bowel Disease and Colorectal Cancer.International journal of biological sciences · 2021Review
- Article
- ISGylation of Hepatitis C Virus NS5A Protein Promotes Viral RNA Replication via Recruitment of Cyclophilin A.Journal of virology · 2020Article
- Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report here a biochemical and structural characterization of domain 2 of the nonstructural 5A protein (NS5A) from the JFH1 Hepatitis C virus strain and its interactions with cyclophilins A and B (CypA and CypB). Gel filtration chromatography, circular dichroism spectroscopy, and finally NMR spectroscopy all indicate the natively unfolded nature of this NS5A-D2 domain. Because mutations in this domain have been linked to cyclosporin A resistance, we used NMR spectroscopy to investigate potential interactions between NS5A-D2 and cellular CypA and CypB. We observed a direct molecular interaction between NS5A-D2 and both cyclophilins. The interaction surface on the cyclophilins corresponds to their active site, whereas on NS5A-D2, it proved to be distributed over the many proline residues of the domain. NMR heteronuclear exchange spectroscopy yielded direct evidence that many proline residues in NS5A-D2 form a valid substrate for the enzymatic peptidyl-prolyl cis/trans isomerase (PPIase) activity of CypA and CypB.
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Registered trials
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.