The domain 2 of the HCV NS5A protein is intrinsically unstructured.
We present here our current understanding of the NS5A-D2 domain of the hepatitis C virus. Whereas this protein domain is globally unstructured as assessed by macroscopic techniques such as size exclusion chromatography, circular dichroism and homonuclear NMR spectroscopy, high resolution triple resonance spectroscopy allows the identification of a small region of residual structure. This region corresponds moreover to the most conserved sequence over the different genotypes of the virus, underscoring its functional importance. We show that it forms an anchoring point for the host cell cyclophilin prolyl cis/trans isomerase, providing a molecular basis for the use of cyclophilin inhibitors in an antiviral strategy.
Hanoulle
Xavier
X
Unité de glycobiologie Structurale et Fonctionnelle, UMR 8576 CNRS, IFR 147, Université Lille1 - Sciences et Technologies, 59655 Villeneuve d'Ascq, France. Xavier.hanoulle@univ-lille1.fr
Badillo
Aurelie
A
Verdegem
Dries
D
Penin
François
F
Lippens
Guy
G
D000998:Antiviral Agents / Q000737:chemistry; D021983:Cyclophilins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016174:Hepacivirus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D021983:Cyclophilins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase