PHOSPHOLIPID INTERACTIONS OF A PEPTIDE FROM THE FUSION-RELATED DOMAINOF THE GLYCOPROTEIN OF VHSV, A FISH RHABDOVIRUS

Previous studies mapped a p2 domain (aa 82-109) which binds phosphatid ylserine (PS) (Estepa and Cell, 1996a) and contains three contiguous h ydrophobic amino acid heptad repeats followed by a positively charged stretch (Coll, 1995b) in the glycoprotein G of the viral hemorrhagic s epticemia virus (VHSV), a fish rhabdovirus. Anti-p2 antibodies inhibit ed low-ph VHSV-induced fusion (Estepa and Cell, 1997) and low-ph PS bi nding to VHSV (Estepa and Cell, 1996a). We report here further studies on the interaction of the synthetic peptide p2 with phospholipid vesi cles. The synthetic p2 peptide was able to mediate aggregation, lipid mixing, and leakage of contents only with negatively charged phospholi pid vesicles and in a concentration-dependent manner. As shown by its effect on lipid phase transitions deduced from data with fluorescence polarization and differential scanning calorimetry, the p2 peptide bec omes inserted into the hydrophobic negatively charged phospholipid ves icle bilayers. In addition, data based on circular dichroism showed th at the p2 peptide folds as a structure with a high content of beta-she ets stabilized by interaction with anionic phospholipids. These studie s are potentially relevant to viral fusion in VHSV. (C) 1998 Academic Press.