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Publication Abstract from PubMed

Antibodies can have an impact on HIV-1 infection in multiple ways, including antibody-dependent cellular cytotoxicity (ADCC), a correlate of protection observed in the RV144 vaccine trial. One of the most potent ADCC-inducing epitopes on HIV-1 Env is recognized by the C11 antibody. Here, we present the crystal structure, at 2.9 A resolution, of the C11-like antibody N12-i3, in a quaternary complex with the HIV-1 gp120, a CD4-mimicking peptide M48U1, and an A32-like antibody, N5-i5. Antibody N12-i3 recognizes an epitope centered on the N-terminal "eighth strand" of a critical beta sandwich, which our analysis indicates to be emblematic of a late-entry state, after the gp120 detachment. In prior entry states, this sandwich comprises only seven strands, with the eighth strand instead pairing with a portion of the gp120 C terminus. The conformational gymnastics of HIV-1 gp120 thus includes altered beta-strand pairing, possibly to reduce immunogenicity, although nevertheless still recognized by the human immune system.

Targeting the Late Stage of HIV-1 Entry for Antibody-Dependent Cellular Cytotoxicity: Structural Basis for Env Epitopes in the C11 Region.,Tolbert WD, Gohain N, Alsahafi N, Van V, Orlandi C, Ding S, Martin L, Finzi A, Lewis GK, Ray K, Pazgier M Structure. 2017 Nov 7;25(11):1719-1731.e4. doi: 10.1016/j.str.2017.09.009. Epub, 2017 Oct 19. PMID:29056481^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.