Cormier E G, Persuh M, Thompson D A, Lin S W, Sakmar T P, Olson W C, Dragic T
Albert Einstein College of Medicine, Microbiology and Immunology Department, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5762-7. doi: 10.1073/pnas.97.11.5762.
The HIV-1 envelope glycoprotein gp120 interacts consecutively with CD4 and the CCR5 coreceptor to mediate the entry of certain HIV-1 strains into target cells. Acidic residues and sulfotyrosines in the amino-terminal domain (Nt) of CCR5 are crucial for viral fusion and entry. We tested the binding of a panel of CCR5 Nt peptides to different soluble gp120/CD4 complexes and anti-CCR5 mAbs. The tyrosine residues in the peptides were sulfated, phosphorylated, or unmodified. None of the gp120/CD4 complexes associated with peptides containing unmodified or phosphorylated tyrosines. The gp120/CD4 complexes containing envelope glycoproteins from isolates that use CCR5 as a coreceptor associated with Nt peptides containing sulfotyrosines but not with peptides containing sulfotyrosines in scrambled Nt sequences. Finally, only peptides containing sulfotyrosines inhibited the entry of an R5 isolate. Our data show that proper posttranslational modification of the CCR5 Nt is required for gp120 binding and viral entry. More importantly, the Nt domain determines the specificity of the interaction between CCR5 and gp120s from isolates that use this coreceptor.
人类免疫缺陷病毒1型包膜糖蛋白gp120与CD4及CCR5共受体依次相互作用，介导某些HIV-1毒株进入靶细胞。CCR5氨基末端结构域（Nt）中的酸性残基和磺基酪氨酸对于病毒融合和进入至关重要。我们测试了一组CCR5 Nt肽与不同可溶性gp120/CD4复合物及抗CCR5单克隆抗体的结合情况。肽中的酪氨酸残基进行了硫酸化、磷酸化或未修饰处理。没有一种gp120/CD4复合物与含有未修饰或磷酸化酪氨酸的肽相关联。含有以CCR5作为共受体的分离株包膜糖蛋白的gp120/CD4复合物与含有磺基酪氨酸的Nt肽相关联，但与Nt序列混乱且含有磺基酪氨酸的肽不相关联。最后，只有含有磺基酪氨酸的肽能抑制R5分离株的进入。我们的数据表明，CCR5 Nt的适当翻译后修饰是gp120结合和病毒进入所必需的。更重要的是，Nt结构域决定了CCR5与使用该共受体的分离株的gp120之间相互作用的特异性。
