Interaction of the most membranotropic region of the HCV E2 envelope glycoprotein with membranes. Biophysical characterization
Ana J Pérez-Berná 1, Jaime Guillén 1, Miguel R Moreno 2, Ana I Gómez-Sànchez 2, Georg Pabst 3, Peter Laggner 3 and José Villalaín 4*
1 Universidad "Miguel Hernández"
2 Universidad "Miguel Hernàndez"
3 Austrian Academy Sciences Graz
4 Universidad Miguel Hernandez /Campus de Elche
* To whom correspondence should be addressed. E-mail: jvillalain{at}umh.es.
Submitted on December 3, 2007
Revised on January 24, 2008
Accepted on 21 February 2008
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Abstract |
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The previously identified membrane-active regions of the HCV E1 and E2 envelope glycoproteins led us to identify different segments which 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 as well as membrane fusion. Consequently, we have carried out a study of the binding and interaction with the lipid bilayer of a peptide corresponding to segment 603-634, peptide E2FP, as well as the structural changes which take place in both the peptide and the phospholipid molecules induced by membrane binding through a series of complementary experiments. Here we demonstrate that peptide E2FP binds to and interacts with phospholipid model membranes, modulates the polymorphic phase behavior of membrane phospholipids, it is localized in a shallow position in the membrane and it is probably oligomerized in the presence of membranes. These data support its role in HCV-mediated membrane fusion, and would sustain the notion that this segment of the E2 envelope glycoprotein, together with other segments of E2 and E1 glycoproteins, provide the driving force for the merging of the viral and target cell membranes.
Key Words:
HCV E2 glycoprotein, Membrane fusion, Peptide-lipid interaction
