Conformation of membrane fusion-active 20-residue peptides with or without lipid bilayers. Implication of alpha-helix formation for membrane fusion.

Fusion of small unilamellar vesicles of egg phosphatidylcholine can be triggered with synthetic 20-residue peptides. Taking the N-terminal amino acid sequence of HA-2 polypeptide of influenza virus as a guideline, we designed and synthesized several peptides having amphiphilic structures. Among the peptides so far studied, those active to induce membrane fusion took an alpha-helical conformation in the presence of phospholipid bilayers, while a peptide which was unable to induce membrane fusion was in a beta-structure. Mixing of a pair of positively and negatively charged peptides, which had a complementary arrangement of electric charges to each other, resulted in alpha-helix formation at neutral pH, the condition of forming a randomly coiled conformation for each peptide. We concluded that alpha-helix formation was one of the necessary conditions to trigger a process of membrane fusion, at least in the present set of peptides. Characteristic features of these amphiphilic peptides are also described.