Hepatitis C virus NS5A protein is a substrate for the Peptidyl-Prolyl cis/trans isomerase activity of Cyclophilins A and B. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2009

Hepatitis C virus NS5A protein is a substrate for the Peptidyl-Prolyl cis/trans isomerase activity of Cyclophilins A and B.

Résumé

We report a biochemical and structural characterization of domain 2 of the non-structural 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 (CsA) 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 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.

Dates et versions

hal-00373457 , version 1 (06-04-2009)

Identifiants

Citer

Xavier Hanoulle, Aurélie Badillo, Jean-Michel Wieruszeski, Dries Verdegem, Isabelle Landrieu, et al.. Hepatitis C virus NS5A protein is a substrate for the Peptidyl-Prolyl cis/trans isomerase activity of Cyclophilins A and B.. Journal of Biological Chemistry, 2009, epub ahead of print. ⟨10.1074/jbc.M809244200⟩. ⟨hal-00373457⟩
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