Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env.
Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env.
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DOI：
10.1038/ncomms7144
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发表时间：
2015-02-05
影响因子：
16.6
通讯作者：
Lee KK
中科院分区：
文献类型：
--
作者：
Guttman M;Cupo A;Julien JP;Sanders RW;Wilson IA;Moore JP;Lee KK
HIV的包膜糖蛋白（Env）是中和抗体的唯一靶标。已经报道了与截短的Env亚基或组分复合的许多广泛中和抗体（bNAb）的结构。然而，它们与完整的Env三聚体的相互作用，以及在这种更天然的背景下构成中和抗性的结构决定因素还不太清楚。在这里，我们使用氢/氘交换来检查一组bNAb和天然样Env三聚体（SOSIP.664三聚体）之间的相互作用。高效力的bNAb仅在其结合界面处引起局部效应，而效力较低的抗体的结合与整个三聚体的精细变化相关。结合动力学，我们的研究结果表明，弱中和抗体只能结合时，三聚体瞬时样品开放状态。我们建议，这种开放运动的动力学各不相同的分离株，与Env从中和敏感的病毒开放更频繁比Env从耐药病毒。
HIV’s envelope glycoprotein (Env) is the sole target for neutralizing antibodies. The structures of many broadly neutralizing antibodies (bNAbs) in complex with truncated Env subunits or components have been reported. However, their interaction with the intact Env trimer, and the structural determinants that underlie neutralization resistance in this more native context are less well understood. Here we use hydrogen/deuterium-exchange to examine the interactions between a panel of bNAbs and native-like Env trimers (SOSIP.664 trimers). Highly potent bNAbs cause only localized effects at their binding interface, while the binding of less potent antibodies is associated with elaborate changes throughout the trimer. In conjunction with binding kinetics, our results suggest that poorly neutralizing antibodies can only bind when the trimer transiently samples an open state. We propose that the kinetics of such opening motions varies among isolates, with Env from neutralization-sensitive viruses opening more frequently than Env from resistant viruses.
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影响因子：
64.8
作者：
Liu, Jun;Bartesaghi, Alberto;Borgnia, Mario J.;Sapiro, Guillermo;Subramaniam, Sriram
通讯作者：
Subramaniam, Sriram
DOI：
10.1073/pnas.96.11.6359
发表时间：
1999-05-25
影响因子：
11.1
作者：
Hoffman, TL;LaBranche, CC;Doms, RW
通讯作者：
Doms, RW
影响因子：
14.9
作者：
Eroshkin AM;LeBlanc A;Weekes D;Post K;Li Z;Rajput A;Butera ST;Burton DR;Godzik A
通讯作者：
Godzik A
影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF
影响因子：
6.7
作者：
Julien JP;Sok D;Khayat R;Lee JH;Doores KJ;Walker LM;Ramos A;Diwanji DC;Pejchal R;Cupo A;Katpally U;Depetris RS;Stanfield RL;McBride R;Marozsan AJ;Paulson JC;Sanders RW;Moore JP;Burton DR;Poignard P;Ward AB;Wilson IA
通讯作者：
Wilson IA