title: Interaction of the most membranotropic region of the HCV E2 envelope glycoprotein with membranes. Biophysical characterization.
abstract: The previously identified membrane-active regions of the hepatitis C virus (HCV) E1 and E2 envelope glycoproteins led us to identify different segments that might be implicated in viral membrane fusion, membrane interaction, and/or protein-protein binding. HCV E2 glycoprotein contains one of the most membranotropic segments, segment 603-634, which has been implicated in CD81 binding, E1/E2 and E2/E2 dimerization, and membrane interaction. Through a series of complementary experiments, we have carried out a study of the binding and interaction with the lipid bilayer of a peptide corresponding to segment 603-634, peptide E2(FP), as well as the structural changes induced by membrane binding that take place in both the peptide and the phospholipid molecules. Here, we demonstrate that peptide E2(FP) binds to and interacts with phospholipid model membranes, modulates the polymorphic phase behavior of membrane phospholipids, is localized in a shallow position in the membrane, and is probably oligomerized in the presence of membranes. These data support the role of E2(FP) in HCV-mediated membrane fusion, and sustain the notion that this segment of the E2 envelope glycoprotein, together with other segments of E2 and E1 glycoproteins, provides the driving force for the merging of the viral and target cell membranes.
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche-Alicante, Spain.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Pérez-Berná
authors.forename: Jaime
authors.initials: J
authors.lastname: Guillén
authors.forename: Miguel R
authors.initials: MR
authors.lastname: Moreno
authors.forename: Ana I
authors.initials: AI
authors.lastname: Gómez-Sánchez
authors.forename: George
authors.initials: G
authors.lastname: Pabst
authors.forename: Peter
authors.initials: P
authors.lastname: Laggner
authors.forename: José
authors.initials: J
authors.lastname: Villalaín
mesh_terms: D001665:Binding Sites; D008051:Lipid Bilayers / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus