Fujii G, Horvath S, Woodward S, Eiserling F, Eisenberg D
Molecular Biology Institute, University of California, Los Angeles 90024-1570.
Protein Sci. 1992 Nov;1(11):1454-64. doi: 10.1002/pro.5560011107.
The mechanism of protein-mediated membrane fusion and lysis has been investigated by solution-state studies of the effects of peptides on liposomes. A peptide (SI) corresponding to a highly amphiphilic C-terminal segment from the envelope protein (gp41) of the human immunodeficiency virus (HIV) was synthesized and tested for its ability to cause lipid membranes to fuse together (fusion) or to break open (lysis). These effects were compared to those produced by the lytic and fusogenic peptide from bee venom, melittin. Other properties studied included the changes in visible absorbance and mean particle size, and the secondary structure of peptides as judged by CD spectroscopy. Taken together, the observations suggest that protein-mediated membrane fusion is dependent not only on hydrophobic and electrostatic forces but also on the spatial arrangement of the amino acid residues to form an amphiphilic structure that promotes the mixing of the lipids between membranes. A speculative molecular model is proposed for membrane fusion by alpha-helical peptides, and its relationship to the forces involved in protein-membrane interactions is discussed.
通过肽对脂质体作用的溶液状态研究，对蛋白质介导的膜融合和裂解机制进行了探究。合成了一种与人免疫缺陷病毒（HIV）包膜蛋白（gp41）高度两亲性的C末端片段相对应的肽（SI），并测试了其使脂质膜融合在一起（融合）或破裂（裂解）的能力。将这些效应与蜂毒溶血肽和促融肽所产生的效应进行了比较。研究的其他特性包括可见光吸收和平均粒径的变化，以及通过圆二色光谱法判断的肽的二级结构。综合来看，这些观察结果表明，蛋白质介导的膜融合不仅取决于疏水和静电力，还取决于氨基酸残基的空间排列，以形成促进膜间脂质混合的两亲性结构。提出了一种关于α-螺旋肽介导膜融合的推测性分子模型，并讨论了其与蛋白质-膜相互作用中所涉及的力的关系。
