MEMBRANE ORIENTATION OF THE SIV FUSION PEPTIDE DETERMINES ITS EFFECT ON BILAYER STABILITY AND ABILITY TO PROMOTE MEMBRANE-FUSION

The amino terminal segment of the gp32 glycoprotein of SIV has been id entified as an important region for membrane fusion. A synthetic dodec apeptide corresponding to this amino terminal segment, SIVwt, can prom ote the fusion of liposomes. This peptide inserts at an oblique angle into the membrane. If the amino acid sequence of this peptide is chang ed, while maintaining the same amino acid composition, the resulting p eptide, SIVmutV, no longer promotes fusion and it is oriented perpendi cular to the plane of the bilayer. In the present work we demonstrate that SIVwt, but not SIVmutV, can lower the bilayer to hexagonal phase transition temperature of model membranes composed of dipalmitoleoyl p hosphatidylethanolamine. In addition the SIVwt formation of structures which give rise to isotropic P-31 NMR signals in mixtures with monome thyldioleoyl phosphatidylethanolamine. These structures are not formed with SIVmutV and their formation with SIVwt is suppressed with lysoph ospatidylcholine. Taken together these results suggest that the observ ed correlation between oblique insertion of viral fusion peptides into membranes and their fusogenicity may be a consequence on these peptid es increasing negative monolayer curvature. (C) 1994 Academic Press, I nc.