title: Membrane-perturbing properties of three peptides corresponding to the ectodomain of hepatitis C virus E2 envelope protein.
abstract: Based on the predicted capacity to interact with membranes at the interface, we have found three regions in the ectodomain of the hepatitis C virus envelope glycoprotein E2 (430-449, 543-560 and 603-624) with the ability to destabilize membranes. Three peptides corresponding to the sequence of these regions have been synthesized and their interaction with liposomes have been characterized. The three peptides were able to insert deeply into the hydrophobic core of negatively charged phospholipids as stated by fluorescence depolarization of the probe 1,6-diphenyl-1,3,5-hexatriene. Peptides E2(430-449) and E2(603-624) were able to induce aggregation of phosphatidylglycerol vesicles in a concentration-dependent manner both at neutral and acidic pH while peptide E2(543-560) did not induce any increase of optical density at 360 nm in the concentration range studied. The three peptides induced lipid mixing and the release of the internal contents in a dose-dependent manner when acidic phospholipids were used. Fourier transformed infrared spectroscopy indicated that the peptides adopted mainly a beta-sheet conformation which is not modified by the presence of acidic phospholipids. Taken together, our results point out to the involvement of these three regions in the fusion mechanism of HCV at the plasma membrane level.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pacheco
authors.forename: Julián
authors.initials: J
authors.lastname: Gómez-Gutiérrez
authors.forename: Belén
authors.initials: B
authors.lastname: Yélamos
authors.forename: Carmen
authors.initials: C
authors.lastname: Delgado
authors.forename: Fernando
authors.initials: F
authors.lastname: Roncal
authors.forename: Juan P
authors.initials: JP
authors.lastname: Albar
authors.forename: Darrell
authors.initials: D
authors.lastname: Peterson
authors.forename: Francisco
authors.initials: F
authors.lastname: Gavilanes
mesh_terms: D002462:Cell Membrane / Q000502:physiology; D005454:Fluorescence Polarization; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus