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.