6BCK
Crystal Structure of Broadly Neutralizing Antibody N49P7 in Complex with HIV-1 Clade AE strain 93TH057 gp120 core.
Summary for 6BCK
| Entry DOI | 10.2210/pdb6bck/pdb |
| Descriptor | clade A/E 93TH057 HIV-1 gp120 core, N49P7 Fab heavy chain of N29P7 IgG, N49P7 Fab light chain from N49P7 IgG, ... (6 entities in total) |
| Functional Keywords | hiv-1, vrc01-class antibody, cd4 binding site, clade a/e 93th057 gp120, viral protein-immune system complex, n49p7, immune system, viral protein/immune system |
| Biological source | Human immunodeficiency virus 1 More |
| Total number of polymer chains | 3 |
| Total formula weight | 88350.98 |
| Authors | Tolbert, W.D.,Gohain, N.,Pazgier, M. (deposition date: 2017-10-20, release date: 2018-05-23, Last modification date: 2024-10-23) |
| 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 Cited by 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: 29731169DOI: 10.1016/j.cell.2018.03.061 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
Download full validation report
