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Status: Bibliographieeintrag

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Verfasst von:Verdegem, Dries [VerfasserIn]   i
 Badillo, Aurélie [VerfasserIn]   i
 Wieruszeski, Jean-Michel [VerfasserIn]   i
 Landrieu, Isabelle [VerfasserIn]   i
 Leroy, Arnaud [VerfasserIn]   i
 Bartenschlager, Ralf [VerfasserIn]   i
 Penin, François [VerfasserIn]   i
 Lippens, Guy [VerfasserIn]   i
 Hanoulle, Xavier [VerfasserIn]   i
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

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