Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation

• DOI: 10.1038/s41467-021-21816-x
• Publication Date: 2021-03-29T10:04:22Z
• Authors: Claudia A. Jette; Christopher O. Ba...; Sharon M. Kirk; Bruno Melillo; Amos B. Smith; Pamela J. Bjorkman
• Keywords: Trimer

Abstract Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions people. Entry into target cells is mediated by 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 Env inserting conserved pocket on subunit gp120. Here, we present single-particle cryo-EM structures CD4-mimetics BNM-III-170 M48U1 bound BG505 native-like trimer plus CD4-induced antibody 17b at 3.7 Å 3.9 resolution, respectively. CD4-mimetic-bound exhibits canonical including opening, formation 4-stranded gp120 bridging sheet, displacement V1V2 loop, compact elongated gp41 HR1C helical bundle. We conclude that structural both subunits are induced pocket.