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Title | Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 1950, Year 2021 |
Publish date | Mar 29, 2021 |
Authors | Claudia A Jette / Christopher O Barnes / Sharon M Kirk / Bruno Melillo / Amos B Smith / Pamela J Bjorkman / |
PubMed Abstract | Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host ...Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4's Phe43 interaction with Env by inserting into the conserved Phe43 pocket on Env subunit gp120. Here, we present single-particle cryo-EM structures of CD4-mimetics BNM-III-170 and M48U1 bound to a BG505 native-like Env trimer plus the CD4-induced antibody 17b at 3.7 Å and 3.9 Å resolution, respectively. CD4-mimetic-bound BG505 exhibits canonical CD4-induced conformational changes including trimer opening, formation of the 4-stranded gp120 bridging sheet, displacement of the V1V2 loop, and formation of a compact and elongated gp41 HR1C helical bundle. We conclude that CD4-induced structural changes on both gp120 and gp41 Env subunits are induced by binding to the gp120 Phe43 pocket. |
External links | Nat Commun / PubMed:33782388 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.9 Å |
Structure data | EMDB-23462, PDB-7lo6: EMDB-23465, PDB-7lok: |
Chemicals | ChemComp-NAG: ChemComp-5VG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / CD4m / fusion / HIV-1 / entry / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / membrane |