HIV-1 Envelope Conformation, Allostery, and Dynamics.

HIV-1 Envelope Conformation, Allostery, and Dynamics.
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DOI:
10.3390/v13050852
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发表时间:
2021-05-07
期刊:
Viruses
影响因子:
--
通讯作者:
Henderson R
Henderson R
中科院分区:
其他
文献类型:
--
作者:
Bennett AL;Henderson R

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HIV-1包膜糖蛋白(Env)介导宿主细胞融合,是HIV-1疫苗设计的主要靶标。Env在与其宿主细胞受体CD 4接合时经历一系列功能上重要的构象重排。作为广泛中和抗体的唯一靶标,我们对这些转变的理解在疫苗免疫原设计中起着关键作用。在这里,我们回顾现有的实验数据询问HIV-1 Env的构象和详细的计算工作,旨在描绘一系列的构象变化连接这些重排。这些研究提供了融合前封闭,开放和过渡中间结构,控制重排的变构元素,和状态到状态的过渡动力学的结构映射。这些研究和分子建模创新的结合为以更高的空间和时间分辨率研究重排奠定了基础。
The HIV-1 envelope glycoprotein (Env) mediates host cell fusion and is the primary target for HIV-1 vaccine design. The Env undergoes a series of functionally important conformational rearrangements upon engagement of its host cell receptor, CD4. As the sole target for broadly neutralizing antibodies, our understanding of these transitions plays a critical role in vaccine immunogen design. Here, we review available experimental data interrogating the HIV-1 Env conformation and detail computational efforts aimed at delineating the series of conformational changes connecting these rearrangements. These studies have provided a structural mapping of prefusion closed, open, and transition intermediate structures, the allosteric elements controlling rearrangements, and state-to-state transition dynamics. The combination of these investigations and innovations in molecular modeling set the stage for advanced studies examining rearrangements at greater spatial and temporal resolution.
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