| Online-Ressource |
Verfasst von: | Verdegem, Dries [VerfasserIn]  |
| Badillo, Aurélie [VerfasserIn]  |
| Wieruszeski, Jean-Michel [VerfasserIn]  |
| Landrieu, Isabelle [VerfasserIn]  |
| Leroy, Arnaud [VerfasserIn]  |
| Bartenschlager, Ralf [VerfasserIn]  |
| Penin, François [VerfasserIn]  |
| Lippens, Guy [VerfasserIn]  |
| Hanoulle, Xavier [VerfasserIn]  |
Titel: | Domain 3 of NS5A protein from the hepatitis C virus has intrinsic α-helical propensity and is a substrate of cyclophilin A |
Verf.angabe: | Dries Verdegem, Aurélie Badillo, Jean-Michel Wieruszeski, Isabelle Landrieu, Arnaud Leroy, Ralf Bartenschlager, François Penin, Guy Lippens, and Xavier Hanoulle |
E-Jahr: | 2011 |
Jahr: | 13 April 2011 |
Umfang: | 14 S. |
Fussnoten: | Gesehen am 07.12.2022 |
Titel Quelle: | Enthalten in: The journal of biological chemistry |
Ort Quelle: | Bethesda, Md. : ASBMB Publications, 1905 |
Jahr Quelle: | 2011 |
Band/Heft Quelle: | 286(2011), 23, Seite 20441-20454 |
ISSN Quelle: | 1083-351X |
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. |
DOI: | doi:10.1074/jbc.M110.182436 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1074/jbc.M110.182436 |
| Volltext: https://www.sciencedirect.com/science/article/pii/S0021925819491114 |
| DOI: https://doi.org/10.1074/jbc.M110.182436 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | HCV |
| NMR |
| Prolyl Isomerase |
| Protein Domains |
| Protein Structure |
| Protein-Protein Interactions |
K10plus-PPN: | 1826466568 |
Verknüpfungen: | → Zeitschrift |
Domain 3 of NS5A protein from the hepatitis C virus has intrinsic α-helical propensity and is a substrate of cyclophilin A / Verdegem, Dries [VerfasserIn]; 13 April 2011 (Online-Ressource)