IDENTIFICATION OF INDIVIDUAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 AMINO-ACIDS IMPORTANT FOR CD4 RECEPTOR-BINDING
IDENTIFICATION OF INDIVIDUAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 AMINO-ACIDS IMPORTANT FOR CD4 RECEPTOR-BINDING
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DOI：
10.1128/jvi.64.12.5701-5707.1990
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发表时间：
1990-12-01
影响因子：
5.4
通讯作者：
SODROSKI, J
中科院分区：
文献类型：
--
作者：
OLSHEVSKY, U;HELSETH, E;SODROSKI, J
人免疫缺陷病毒1型gp 120外囊膜糖蛋白与CD 4受体的结合对于病毒进入和细胞病变效应是重要的。为了研究gp 120糖蛋白的CD 4结合区域，我们改变了gp 120的氨基酸，不包括半胱氨酸，这些氨基酸在利用CD 4受体的灵长类免疫缺陷病毒中是保守的。两个疏水区（保守区2中的Thr-257和保守区4中的Trp-427）和两个亲水区（保守区3中的Asp-368和Glu-370以及保守区4中的Asp-457）的变化导致CD 4结合显著降低。对于大多数影响这些残基的突变，所观察到的对CD 4结合的影响并没有明显导致全球构象破坏的gp 120分子，评估前体加工，亚基协会，和单克隆抗体识别的测量。这两个亲水性区域表现出强烈的β-转角形成，被预测作为有效的B细胞表位，并位于邻近高变，糖基化的区域。这项研究定义了少量的gp 120残基的重要CD 4结合，其中一些可能构成有吸引力的目标免疫干预。
The binding of the CD4 receptor by the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein is important for virus entry and cytopathic effect. To investigate the CD4-binding region of the gp120 glycoprotein, we altered gp120 amino acids, excluding cysteines, that are conserved among the primate immunodeficiency viruses utilizing the CD4 receptor. Changes in two hydrophobic regions (Thr-257 in conserved region 2 and Trp-427 in conserved region 4) and two hydrophilic regions (Asp-368 and Glu-370 in conserved region 3 and Asp-457 in conserved region 4) resulted in significant reductions in CD4 binding. For most of the mutations affecting these residues, the observed effects on CD4 binding did not apparently result from global conformational disruption of the gp120 molecule, as assessed by measurements of precursor processing, subunit association, and monoclonal antibody recognition. The two hydrophilic regions exhibit a strong propensity for .beta.-turn formation, are predicted to act as efficient B-cell epitopes, and are located adjacent to hypervariable, glycosylated regions. This study defines a small number of gp120 residues important for CD4 binding, some of which might constitute attractive targets for immonulogic intervention.