Structural and functional analysis of the HCV p7 protein.
The p7 membrane polypeptide from HCV is essential for virus infection. It exhibits ion-channel activity reported to be specifically blocked by various compounds. These properties make p7 an attractive candidate target for antiviral intervention to combat viral hepatitis C infection. In this context, in vitro functional analyses of isolated p7 coupled to structural characterization are critical for further understanding of the molecular mechanisms of p7 ion-channel activity and for the development of new antiviral drugs. We present here in vitro assays designed to purify synthetic p7 by RP-HPLC, to investigate its ion-channel properties by means of planar lipid-bilayer assays and patch-clamp recordings after reconstitution into liposomes, and to analyze its structural features by circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular dynamics (MD).
Saint
Nathalie
N
Centre de Biochimie Structurale, Université de Montpellier I et II, Montpellier, France.
Montserret
Roland
R
Chipot
Christophe
C
Penin
François
F
D000998:Antiviral Agents / Q000494:pharmacology; D040761:Biomimetic Materials / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D016174:Hepacivirus / Q000187:drug effects / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018408:Patch-Clamp Techniques; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D014764:Viral Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D000086082:Viroporin Proteins
D000998:Antiviral Agents; D008051:Lipid Bilayers; D008081:Liposomes; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins