Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120.
Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120.
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DOI：
10.1126/science.1175868
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发表时间：
2009-11-20
期刊：
影响因子：
--
通讯作者：
Kwong PD
中科院分区：
文献类型：
--
作者：
Chen L;Kwon YD;Zhou T;Wu X;O'Dell S;Cavacini L;Hessell AJ;Pancera M;Tang M;Xu L;Yang ZY;Zhang MY;Arthos J;Burton DR;Dimitrov DS;Nabel GJ;Posner MR;Sodroski J;Wyatt R;Mascola JR;Kwong PD
HIV-1 gp120上与CD4受体结合的位点容易受到抗体的攻击。然而，大多数与该位点相互作用的抗体不能中和HIV-1。为了了解这种耐药性的基础，我们确定了与gp120配合物中两种低中和的cd4结合位点（CD4BS）抗体F105和b13的共晶结构。这两种抗体对gp120的进近角与CD4和一种罕见的、广泛中和的CD4BS抗体b12相似。然而，与b12结合的gp120相比，识别上的细微差异导致F105-和b13结合的构象存在实质性差异。建模和结合实验表明，这些构象与病毒刺突的相容性很差。这种不相容是CD4BS识别的微小差异的结果，使得HIV-1除了对最精确的靶向抗体外，对所有抗体都具有抗性。
The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4–binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.
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影响因子：
64.8
作者：
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通讯作者：
Subramaniam, Sriram
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