Rabut G E, Konner J A, Kajumo F, Moore J P, Dragic T
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
J Virol. 1998 Apr;72(4):3464-8. doi: 10.1128/JVI.72.4.3464-3468.1998.
Multiple extracellular domains of the CC-chemokine receptor CCR5 are important for its function as a human immunodeficiency virus type 1 (HIV-1) coreceptor. We have recently demonstrated by alanine scanning mutagenesis that the negatively charged residues in the CCR5 amino-terminal domain are essential for gp120 binding and coreceptor function. We have now extended our analysis of this domain to include most polar and nonpolar amino acids. Replacement of alanine with all four tyrosine residues and with serine-17 and cysteine-20 decrease or abolish gp120 binding and CCR5 coreceptor activity. Tyrosine-15 is essential for viral entry irrespective of the test isolate. Substitutions at some of the other positions impair the entry of dualtropic HIV-1 isolates more than that of macrophagetropic ones.
CC趋化因子受体CCR5的多个细胞外结构域对其作为1型人类免疫缺陷病毒（HIV-1）共受体的功能至关重要。我们最近通过丙氨酸扫描诱变证明，CCR5氨基末端结构域中的带负电荷残基对于gp120结合和共受体功能至关重要。我们现在已将对该结构域的分析扩展至包括大多数极性和非极性氨基酸。用所有四个酪氨酸残基以及丝氨酸-17和半胱氨酸-20取代丙氨酸会降低或消除gp120结合和CCR5共受体活性。无论测试分离株如何，酪氨酸-15对于病毒进入都是必不可少的。其他一些位置的取代对双嗜性HIV-1分离株进入的损害比对巨噬细胞嗜性分离株的损害更大。
