IDENTIFICATION OF THE RESIDUES IN HUMAN CD4 CRITICAL FOR THE BINDING OF HIV
IDENTIFICATION OF THE RESIDUES IN HUMAN CD4 CRITICAL FOR THE BINDING OF HIV
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DOI：
10.1016/0092-8674(89)90922-7
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发表时间：
1989-05-05
期刊：
影响因子：
64.5
通讯作者：
SWEET, RW
中科院分区：
文献类型：
--
作者：
ARTHOS, J;DEEN, KC;SWEET, RW
CD4分子是一种T细胞表面的糖蛋白，它与人类免疫缺陷病毒HIV的包膜糖蛋白高度亲和力地相互作用，从而成为这种病毒的细胞受体。为了确定CD4上与gp120结合所必需的位点，我们产生了几个截短的、可溶的CD4衍生物和一系列26个替代突变体。与截短蛋白的定量结合分析表明，高亲和力结合的决定因素仅存在于CD4的前106个氨基酸(V1结构域)，该区域与免疫球蛋白可变区具有显著的序列同源性。对替换突变体的分析进一步定义了该区域内的离散结合部位，该结合部位与抗体可变区的第二互补决定区在结构上同源的区域重叠。最后，我们证明了可溶性的CD4蛋白对病毒感染和病毒介导的细胞融合的抑制作用依赖于它们与这个结合位点上的gp120的结合。
The CD4 molecule is a T cell surface glycoprotein that interacts with high affinity with the envelope glycoprotein of the human immunodeficiency virus, HIV, thus serving as a cellular receptor for this virus. To define the sites on CD4 essential for binding to gp120, we produced several truncated, soluble derivatives of CD4 and a series of 26 subsitution mutants. Quantitative binding analyses with the truncated proteins demonstrate that the determinants for high affinity binding lie solely with the first 106 amino acids of CD4 (the V1 domain), a region having significant sequence homology to immunoglobulin variable regions. Analysis of the substitution mutants further defines a discrete binding site within this domain that overlaps a region structurally homologous to the second complementarity-determining region of antibody variable domains. Finally, we demonstrate that the inhibition of virus infection and virus-mediated cell fusion by soluble CD4 proteins depends on their association with gp120 at this binding site.