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-Structure paper
Title | HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes. |
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Journal, issue, pages | Nature, Vol. 623, Issue 7989, Page 1026-1033, Year 2023 |
Publish date | Nov 22, 2023 |
Authors | Wenwei Li / Zhuan Qin / Elizabeth Nand / Michael W Grunst / Jonathan R Grover / Julian W Bess / Jeffrey D Lifson / Michael B Zwick / Hemant D Tagare / Pradeep D Uchil / Walther Mothes / |
PubMed Abstract | Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD4. Although high-resolution structures of Env in a ...Human immunodeficiency virus 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein (Env) to the cell-surface receptor CD4. Although high-resolution structures of Env in a complex with the soluble domains of CD4 have been determined, the binding process is less understood in native membranes. Here we used cryo-electron tomography to monitor Env-CD4 interactions at the membrane-membrane interfaces formed between HIV-1 and CD4-presenting virus-like particles. Env-CD4 complexes organized into clusters and rings, bringing the opposing membranes closer together. Env-CD4 clustering was dependent on capsid maturation. Subtomogram averaging and classification revealed that Env bound to one, two and finally three CD4 molecules, after which Env adopted an open state. Our data indicate that asymmetric HIV-1 Env trimers bound to one and two CD4 molecules are detectable intermediates during virus binding to host cell membranes, which probably has consequences for antibody-mediated immune responses and vaccine immunogen design. |
External links | Nature / PubMed:37993716 / PubMed Central |
Methods | EM (subtomogram averaging) |
Resolution | 9.0 - 20.0 Å |
Structure data | EMDB-29292: HIV-1 envelope trimer bound to one CD4 molecule on membranes EMDB-29293: HIV-1 envelope trimer bound to two CD4 molecules on membranes EMDB-29294: HIV-1 envelope trimer bound to three CD4 molecules on membranes EMDB-29295: Consensus structure of HIV-1 envelope trimer bound to CD4 receptors on membranes EMDB-41045: Unliganded HIV-1 Env on virion |
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