5WB9

Crystal structure of CD4 binding site antibody N60P23 in complex with HIV-1 clade A/E strain 93TH057 gp120 core

Summary for 5WB9

• Entry DOI: 10.2210/pdb5wb9/pdb
• Descriptor: clade A/E 93TH057 HIV-1 gp120 core, N60P23 Fab heavy chain, N60P23 Fab light chain, ... (7 entities in total)
• Functional Keywords: cd4 binding site, gp120 core, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 88842.67

Authors

Gohain, N.,Tolbert, W.,Pazgier, M. (deposition date: 2017-06-28, release date: 2018-05-23, Last modification date: 2024-11-13)

Primary citation

Sajadi, M.M.,Dashti, A.,Rikhtegaran Tehrani, Z.,Tolbert, W.D.,Seaman, M.S.,Ouyang, X.,Gohain, N.,Pazgier, M.,Kim, D.,Cavet, G.,Yared, J.,Redfield, R.R.,Lewis, G.K.,DeVico, A.L.
Identification of Near-Pan-neutralizing Antibodies against HIV-1 by Deconvolution of Plasma Humoral Responses.
Cell, 173:1783-1795.e14, 2018

PubMed Abstract: Anti-HIV-1 envelope broadly neutralizing monoclonal antibodies (bNAbs) isolated from memory B cells may not fully represent HIV-1-neutralizing profiles measured in plasma. Accordingly, we characterized near-pan-neutralizing antibodies extracted directly from the plasma of two "elite neutralizers." Circulating anti-gp120 polyclonal antibodies were deconvoluted using proteomics to guide lineage analysis of bone marrow plasma cells. In both subjects, a single lineage of anti-CD4-binding site (CD4bs) antibodies explained the plasma-neutralizing activity. Importantly, members of these lineages potently neutralized 89%-100% of a multi-tier 117 pseudovirus panel, closely matching the specificity and breadth of the circulating antibodies. X-ray crystallographic analysis of one monoclonal, N49P7, suggested a unique ability to bypass the CD4bs Phe43 cavity, while reaching deep into highly conserved residues of Layer 3 of the gp120 inner domain, likely explaining its extreme potency and breadth. Further direct analyses of plasma anti-HIV-1 bNAbs should provide new insights for developing antibody-based antiviral agents and vaccines.

PubMed: 29731169
DOI: 10.1016/j.cell.2018.03.061

Experimental method

X-RAY DIFFRACTION (2.4 Å)