5W4L

Crystal structure of the non-neutralizing and ADCC-potent C11-like antibody N12-i3 in complex with HIV-1 clade A/E gp120, the CD4 mimetic M48U1, and the antibody N5-i5.

Summary for 5W4L

• Entry DOI: 10.2210/pdb5w4l/pdb
• Related: 4H8W 4JZW
• Related PRD ID: PRD_001094
• Descriptor: clade A/E 93TH057 HIV-1 gp120 core, CD4 mimetic peptide M48U1, Antibody N5-i5 Fab heavy chain, ... (9 entities in total)
• Functional Keywords: hiv-1 gp120, clade a/e 93th057, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 285301.18

Authors

Tolbert, W.D.,Gohain, N.,Pazgier, M. (deposition date: 2017-06-12, release date: 2017-11-15, Last modification date: 2023-11-15)

Primary citation

Tolbert, W.D.,Gohain, N.,Alsahafi, N.,Van, V.,Orlandi, C.,Ding, S.,Martin, L.,Finzi, A.,Lewis, G.K.,Ray, K.,Pazgier, M.
Targeting the Late Stage of HIV-1 Entry for Antibody-Dependent Cellular Cytotoxicity: Structural Basis for Env Epitopes in the C11 Region.
Structure, 25:1719-1731.e4, 2017

PubMed Abstract: 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 Å 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 β 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 β-strand pairing, possibly to reduce immunogenicity, although nevertheless still recognized by the human immune system.

PubMed: 29056481
DOI: 10.1016/j.str.2017.09.009

Experimental method

X-RAY DIFFRACTION (2.92 Å)