A minor beta-structured conformation is the active state of a fusion peptide of vesicular stomatitis virus glycoprotein

Entry of enveloped animal viruses into their host cells always depends on a step of membrane fusion triggered by conformational changes in viral envelope glycoproteins. Vesicular stomatitis virus (VSV) infection is mediated by virus spike glycoprotein G, which induces membrane fusion at the acidic environment of the endosomal compartment. in a previous work, we identified a specific sequence in the VSV G protein, comprising the residues 145-164, directly involved in membrane interaction and fusion. in the present work we studied the interaction of pep[145-164] with membranes using NMR to solve the structure of the peptide in two membrane-mimetic systems: SDS micelles and liposomes composed of phosphatidylcholme and phosphatidylserine (PC: PS vesicles). the presence of medium-range NOEs showed that the peptide has a tendency to form N- and C-terminal helical segments in the presence of SDS micelles. Analysis of the chemical shift index indicated helix-coil equilibrium for the C-terminal helix under all conditions studied. At pH 7.0, the N-terminal helix also displayed a helix-coil equilibrium when pep[145-164] was free in solution or in the presence of PC: PS. Remarkably, at the fusogenic pH, the region of the N-terminal helix in the presence of SDS or PC: PS presented a third conformational species that was in equilibrium with the helix and random coil. the N-terminal helix content decreases pH and the minor P-structured conformation becomes more prevalent at the fusogenic pH. These data point to a P-conformation as the fusogenic active structure-which is in agreement with the X-ray structure, which shows a P-hairpin for the region corresponding to pep[145-164]. Copyright (c) 2007 European Peptide Society and John Wiley & Sons, Ltd.Univ Fed Rio de Janeiro, Inst Bioquim Med, Programa Biol Estrutural, BR-21941590 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Ctr Nacl Ressonancia Magnet Nucl Jiri Jonas, BR-21941590 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, BrazilWeb of Scienc