HIV-1 Envelope Conformation, Allostery, and Dynamics.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

HIV Envelope Protein gp41/*chemistry ; HIV-1/*genetics ; env Gene Products, Human Immunodeficiency Virus/*chemistry ; env Gene Products, Human Immunodeficiency Virus/*metabolism; Antibodies, Neutralizing/immunology ; HIV Antibodies/immunology ; HIV Envelope Protein gp41/genetics ; HIV Envelope Protein gp41/immunology ; HIV-1/chemistry ; HIV-1/immunology ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Virus Internalization ; env Gene Products, Human Immunodeficiency Virus/genetics ; env Gene Products, Human Immunodeficiency Virus/immunology

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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R01 AI145687 United States AI NIAID NIH HHS; P30 AI064518 United States AI NIAID NIH HHS

Keywords: HIV-1; allostery; envelope; molecular dynamics; structure

0 (Antibodies, Neutralizing)
0 (HIV Antibodies)
0 (HIV Envelope Protein gp41)
0 (env Gene Products, Human Immunodeficiency Virus)

Date Created: 20210602 Date Completed: 20211216 Latest Revision: 20231111

20231111

PMC8150877

10.3390/v13050852

34067073