ArticleThe Journal of biological chemistry2019
Cyclophilin A allows the allosteric regulation of a structural motif in the disordered domain 2 of NS5A and thereby fine-tunes HCV RNA replication.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 16 citations in OpenAlex.
- Optimization of the antiviral spectrum of cyclophilin inhibitors targeting respiratory viruses.Antimicrobial agents and chemotherapy · 2026Article
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease.Nature communications · 2025Article
- Adapted hepatitis C virus clone infects innate immunity-deficient mouse hepatocytes with minimal human HCV entry factors.JHEP reports : innovation in hepatology · 2025Article
- Characterization of Posttranslationally Modified PHF-1 Tau Peptides Using Gaussian Accelerated Molecular Dynamics Simulation.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.Viruses · 2023Article
- Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes.International journal of molecular sciences · 2022Article
- SelectiveAngewandte Chemie (International ed. in English) · 2022Article
- Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches.Pathogens (Basel, Switzerland) · 2021Review
- Flexibility of Oxidized and Reduced States of the Chloroplast Regulatory Protein CP12 in Isolation and in Cell Extracts.Biomolecules · 2021Article
- Cyclophilin A: a key player for etiological agent infection.Applied microbiology and biotechnology · 2021Review
- Gaussian accelerated molecular dynamics (GaMD): principles and applications.Wiley interdisciplinary reviews. Computational molecular scienceArticle
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Implicated in numerous human diseases, intrinsically disordered proteins (IDPs) are dynamic ensembles of interconverting conformers that often contain many proline residues. Whether and how proline conformation regulates the functional aspects of IDPs remains an open question, however. Here, we studied the disordered domain 2 of nonstructural protein 5A (NS5A-D2) of hepatitis C virus (HCV). NS5A-D2 comprises a short structural motif (PW-turn) embedded in a proline-rich sequence, whose interaction with the human prolyl isomerase cyclophilin A (CypA) is essential for viral RNA replication. Using NMR, we show here that the PW-turn motif exists in a conformational equilibrium between folded and disordered states. We found that the fraction of conformers in the NS5A-D2 ensemble that adopt the structured motif is allosterically modulated both by the
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