A non-canonical binding interface in the crystal structure of HIV-1 gp120 core in complex with CD4.
A non-canonical binding interface in the crystal structure of HIV-1 gp120 core in complex with CD4.
复制标题
HIV-1 gp120 核心与 CD4 复合物晶体结构中的非规范结合界面
DOI：
10.1038/srep46733
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发表时间：
2017-04-21
影响因子：
4.6
通讯作者：
Liu XQ
中科院分区：
文献类型：
--
作者：
Duan LW;Zhang H;Zhao MT;Sun JX;Chen WL;Lin JP;Liu XQ
已经报道了HIV gp 120的许多晶体结构，单独或与受体CD 4和同源抗体一起;然而，没有可用的没有抗体稳定的唯一gp 120/CD 4复合物。在这里，我们报告的gp 120/CD 4复合物的晶体结构，没有艾滋病毒-1 CRF07_BC，在中国流行的菌株的抗体的帮助。有趣的是，除了典型的结合表面，第二个相互作用的界面被确定。对关键残基的诱变研究表明，该界面的稳定性对于Env介导的膜融合的效率是重要的。此外，我们发现，在gp 120不存在的情况下靶向CD 4的广谱中和抗体ibalizumab占据了与gp 120上的第二个界面相同的结合表面。因此，我们确定了在病毒进入期间参与第二gp 120-CD 4相互作用界面的可能性，并且还为中和抗体ibalizumab的广泛活性提供了合理的解释。
Numerous crystal structures of HIV gp120 have been reported, alone or with receptor CD4 and cognate antibodies; however, no sole gp120/CD4 complex without stabilization by an antibody is available. Here, we report a crystal structure of the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a strain circulating in China. Interestingly, in addition to the canonical binding surface, a second interacting interface was identified. A mutagenesis study on critical residues revealed that the stability of this interface is important for the efficiency of Env-mediated membrane fusion. Furthermore, we found that a broad neutralizing antibody, ibalizumab, which targets CD4 in the absence of gp120, occupies the same binding surface as the second interface identified here on gp120. Therefore, we identified the possibility of the involvement of a second gp120-CD4 interaction interface during viral entry, and also provided a reasonable explanation for the broad activity of neutralizing antibody ibalizumab.