Owens R J, Burke C, Rose J K
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Virol. 1994 Jan;68(1):570-4. doi: 10.1128/JVI.68.1.570-574.1994.
A chimeric protein consisting of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) ectodomain joined to the transmembrane and cytoplasmic-tail domains of vesicular stomatitis virus G protein lost the ability to fuse CD4+ HeLa cells yet was transported to the cell surface and cleaved normally. These results suggested some critical role of the HIV gp41 transmembrane or cytoplasmic domain in fusion. Subsequent mutagenic analysis of the HIV-1 Env transmembrane domain revealed that the sequence of amino acid residues from positions 696 to 707 of the transmembrane domain was important for fusion function but was not required for anchoring of the Env protein in the lipid bilayer or for transport to the cell surface. Further analysis indicated that the basic residues at positions 696 and 707 were critical for membrane fusion activity, as was the spacing between these residues. These results demonstrate that in addition to providing an anchoring function, the specific amino acid sequence in the transmembrane domain plays a crucial role in the membrane fusion process.
一种嵌合蛋白，由人类免疫缺陷病毒1型（HIV-1）包膜蛋白（Env）的胞外结构域与水泡性口炎病毒G蛋白的跨膜和胞质尾结构域连接而成，它失去了融合CD4+HeLa细胞的能力，但仍能转运至细胞表面并正常裂解。这些结果表明HIV gp41跨膜或胞质结构域在融合过程中发挥了某些关键作用。随后对HIV-1 Env跨膜结构域进行的诱变分析显示，跨膜结构域中696至707位氨基酸残基的序列对融合功能很重要，但对于Env蛋白锚定在脂质双层中或转运至细胞表面并非必需。进一步分析表明，696和707位的碱性残基对膜融合活性至关重要，这些残基之间的间距也是如此。这些结果表明，跨膜结构域中的特定氨基酸序列除了提供锚定功能外，在膜融合过程中也起着关键作用。
