Characterization of the sequence of interactions of the fusion domain of the simian immunodeficiency virus with membranes - Role of the membrane dipole potential

The simian immunodeficiency virus fusion peptide constitutes a 12-residue N -terminal segment of the gp32 protein that is involved in the fusion betwee n the viral and cellular membranes, facilitating the penetration of the vir us in the host cell. Simian immunodeficiency virus fusion peptide is a hydr ophobic peptide that in Me2SO forms aggregates that contain beta-sheet plea ted structures. When added to aqueous media the peptide forms large colloid al aggregates. In the presence of lipidic membranes, however, the peptide i nteracts with the membranes and causes small changes of the membrane electr ostatic potential as shown by fluorescein phosphatidylethanolamine fluoresc ence. Thioflavin T fluorescence and Fourier transformed infrared spectrosco py measurements reveal that the interaction of the peptide with the membran e bilayer results in complete disassembly of the aggregates originating fro m an Me2SO stock solution. Above a lipid/peptide ratio of about 5, the memb rane disaggregation and water precipitation processes become dependent on t he absolute peptide concentration rather than on the lipid/peptide ratio. A schematic mechanism is proposed, which sheds light on how peptide-peptide interactions can be favored with respect to peptide-lipid interactions at v arious lipid/peptide ratios. These studies are augmented by the use of the fluorescent dye 1-(3-sulfonatopropyl)-4-[beta[2-(di-n-octylamino)-6-naphthy l]vinyl] pyridinium betaine that shows the interaction of the peptide with the membranes has a clear effect on the magnitude of the so-called dipole p otential that arises :From dipolar groups located on the lipid molecules an d oriented water molecules at the membrane-water interface. It is shown tha t the variation of the membrane dipole potential affects the extent of the membrane fusion caused by the peptide and implicates the dipolar properties of membranes in their fusion.