Identification of the membrane-active regions of hepatitis C virus p7 protein: biophysical characterization of the loop region.
We have identified the membrane-active regions of the hepatitis C virus p7 protein by performing an exhaustive study of membrane rupture, hemifusion, and fusion induced by a p7-derived peptide library on model membranes having different phospholipid compositions. We report the identification in p7 of a highly membranotropic region located at the loop domain of the protein. Here, we have investigated the interaction of a peptide patterned after the p7 loop (peptide p7(L)), studying its binding and interaction with the lipid bilayer, and evaluated the binding-induced structural changes of the peptide and the phospholipids. We show that positively rich p7(L) strongly binds to negatively charged phospholipids and it is localized in a shallow position in the bilayer. Furthermore, peptide p7(L) exhibits a high tendency to oligomerize in the presence of phospholipids, which could be the driving force for the formation of the active ion channel. Therefore, our findings suggest that the p7 loop could be an attractive candidate for antiviral drug development, because it could be a target for antiviral compounds that may lead to new vaccine strategies.
Pérez-Berná
Ana J
AJ
Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Alicante, Spain.
Guillén
Jaime
J
Moreno
Miguel R
MR
Bernabeu
Angela
A
Pabst
Georg
G
Laggner
Peter
P
Villalaín
José
J
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
D010446:Peptide Fragments; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins