Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike.
Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike.
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DOI：
10.1038/ncomms9167
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发表时间：
2015-09-25
影响因子：
16.6
通讯作者：
Ward AB
中科院分区：
文献类型：
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作者：
Lee JH;Leaman DP;Kim AS;Torrents de la Peña A;Sliepen K;Yasmeen A;Derking R;Ramos A;de Taeye SW;Ozorowski G;Klein F;Burton DR;Nussenzweig MC;Poignard P;Moore JP;Klasse PJ;Sanders RW;Zwick MB;Wilson IA;Ward AB
最近鉴定的三种针对gp 120-gp 41界面表位的广泛中和抗体（bnAb）扩大了HIV-1包膜糖蛋白（Env）三聚体的靶向表面。通过使用生物化学，生物物理和计算方法，我们映射的两个相关的抗体，3BC 315和3BC 176以前未知的三聚体表位。在9.3 μ m分辨率下与3BC 315 Fab结合的可溶性Env三聚体的冷冻-EM重建揭示了抗体在两个gp 41原体之间结合，并通过加速三聚体衰变来中和病毒。与此相反，bnAb 35 O22在gp 120-gp 41界面结合到部分重叠的四级表位不会诱导衰变。N88处的保守gp 41近端聚糖也显示在3BC 176和3BC 315的结合动力学中起作用。最后，我们的数据表明Env三聚体的动态结构影响bnAb表位的暴露。 包膜糖蛋白（Env）三聚体是HIV-1病毒表面上广泛中和抗体的唯一抗原靶标。在这里，作者表明，两种相关的单克隆抗体结合在gp 41原体之间，并通过加速Env三聚体衰变来中和HIV-1。
The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120–gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120–gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes. The envelope glycoprotein (Env) trimer is the only antigenic target for broadly neutralizing antibodies on the surface of the HIV-1 virus. Here the authors show that two related monoclonal antibodies bind between gp41 protomers and neutralize HIV-1 by accelerating Env trimer decay.