Epand R F, Martin I, Ruysschaert J M, Epand R M
Department of Biochemistry, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Biochem Biophys Res Commun. 1994 Dec 30;205(3):1938-43. doi: 10.1006/bbrc.1994.2897.
The amino terminal segment of the gp32 glycoprotein of SIV has been identified as an important region for membrane fusion. A synthetic dodecapeptide corresponding to this amino terminal segment, SIVwt, can promote the fusion of liposomes. This peptide inserts at an oblique angle into the membrane. If the amino acid sequence of this peptide is changed, while maintaining the same amino acid composition, the resulting peptide, SIVmutV, no longer promotes fusion and it is oriented perpendicular 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 phosphatidylethanolamine. In addition the SIVwt promotes the formation of structures which give rise to isotropic 31P NMR signals in mixtures with monomethyldioleoyl phosphatidylethanolamine. These structures are not formed with SIVmutV and their formation with SIVwt is suppressed with lysophosphatidylcholine. Taken together these results suggest that the observed correlation between oblique insertion of viral fusion peptides into membranes and their fusogenicity may be a consequence on these peptides increasing negative monolayer curvature.
猴免疫缺陷病毒（SIV）的糖蛋白gp32的氨基末端片段已被确定为膜融合的重要区域。一种与该氨基末端片段相对应的合成十二肽SIVwt，能够促进脂质体的融合。该肽以倾斜角度插入膜中。如果在保持相同氨基酸组成的情况下改变该肽的氨基酸序列，所得到的肽SIVmutV则不再促进融合，并且其与双层平面垂直排列。在本研究中，我们证明SIVwt能够降低由二棕榈油酰磷脂酰乙醇胺组成的模型膜从双层相到六方相的转变温度，而SIVmutV则不能。此外，SIVwt促进了与单甲基二油酰磷脂酰乙醇胺混合时产生各向同性31P NMR信号的结构的形成。这些结构在SIVmutV存在时不会形成，并且在溶血磷脂酰胆碱存在的情况下，SIVwt对它们的形成有抑制作用。综合这些结果表明，所观察到的病毒融合肽倾斜插入膜与其融合能力之间的相关性，可能是这些肽增加负单层曲率的结果。
