HIV-1 Envelope Conformation,Allostery, and Dynamics |
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Authors: | Ashley Lauren Bennett Rory Henderson |
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Affiliation: | 1.Duke Human Vaccine Institute, Durham, NC 27710, USA;2.Department of Medicine, Duke University, Durham, NC 27710, USA |
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Abstract: | 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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Keywords: | HIV-1 envelope allostery molecular dynamics structure |
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