Kwong P D, Wyatt R, Robinson J, Sweet R W, Sodroski J, Hendrickson W A
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Nature. 1998 Jun 18;393(6686):648-59. doi: 10.1038/31405.
The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. These interactions initiate a fusion of the viral and cellular membranes. Although gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. The structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene.
人类免疫缺陷病毒（HIV）进入细胞需要病毒外膜糖蛋白gp120与细胞表面的CD4糖蛋白和趋化因子受体依次相互作用。这些相互作用引发病毒膜与细胞膜的融合。尽管gp120能引发病毒中和抗体，但HIV仍能逃避免疫系统。我们已解析出HIV-1 gp120核心与人类CD4的双结构域片段以及阻断趋化因子受体结合的中和抗体的抗原结合片段形成的复合物在2.5埃分辨率下的X射线晶体结构。该结构揭示了充满腔隙的CD4-gp120界面、趋化因子受体的保守结合位点、CD4结合后构象变化的证据、CD4诱导的抗体表位的性质以及免疫逃逸的具体机制。我们的结果为理解HIV进入细胞的复杂生物学过程提供了一个框架，并应指导干预措施的研究。
