7LOK

Structure of CD4 mimetic M48U1 in complex with BG505 SOSIP.664 HIV-1 Env trimer and 17b Fab

Summary for 7LOK

• Entry DOI: 10.2210/pdb7lok/pdb
• Related: 7LO6
• EMDB information: 23462 23465
• Descriptor: Envelope glycoprotein BG505 SOSIP.664 gp120, Envelope Glycoprotein BG505 SOSIP.664 gp41, 17b Fab Light Chain, ... (9 entities in total)
• Functional Keywords: hiv-1, fusion, entry, membrane, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 13
• Total formula weight: 325001.59

Authors

Jette, C.A.,Bjorkman, P.J. (deposition date: 2021-02-10, release date: 2021-04-14)

Primary citation

Jette, C.A.,Barnes, C.O.,Kirk, S.M.,Melillo, B.,Smith III, A.B.,Bjorkman, P.J.
Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation.
Nat Commun, 12:1950-1950, 2021

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 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.

PubMed: 33782388
DOI: 10.1038/s41467-021-21816-x

Experimental method

ELECTRON MICROSCOPY (3.9 Å)