7TFN
Cryo-EM structure of CD4bs antibody Ab1303 in complex with HIV-1 Env trimer BG505 SOSIP.664
Summary for 7TFN
| Entry DOI | 10.2210/pdb7tfn/pdb |
| EMDB information | 25877 |
| Descriptor | Envelope glycoprotein BG505 SOSIP.664 - gp120, 2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose, ... (11 entities in total) |
| Functional Keywords | hiv-1 env, neutralizing antibody, cd4 binding site antibody, 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 | 371403.56 |
| Authors | Yang, Z.,Bjorkman, P.J. (deposition date: 2022-01-06, release date: 2022-01-19, Last modification date: 2024-10-30) |
| Primary citation | Yang, Z.,Dam, K.A.,Bridges, M.D.,Hoffmann, M.A.G.,DeLaitsch, A.T.,Gristick, H.B.,Escolano, A.,Gautam, R.,Martin, M.A.,Nussenzweig, M.C.,Hubbell, W.L.,Bjorkman, P.J. Neutralizing antibodies induced in immunized macaques recognize the CD4-binding site on an occluded-open HIV-1 envelope trimer. Nat Commun, 13:732-732, 2022 Cited by PubMed Abstract: Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when Env trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both antibodies recognize the CD4bs on Env trimer with an 'occluded-open' conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4. The occluded-open Env trimer conformation includes outwardly-rotated gp120 subunits, but unlike CD4-bound Envs, does not exhibit V1V2 displacement, 4-stranded gp120 bridging sheet, or co-receptor binding site exposure. Inter-protomer distances within trimers measured by double electron-electron resonance spectroscopy suggest an equilibrium between occluded-open and closed Env conformations, consistent with Ab1303/Ab1573 binding stabilizing an existing conformation. Studies of Ab1303/Ab1573 demonstrate that CD4bs neutralizing antibodies that bind open Env trimers can be raised by immunization, thereby informing immunogen design and antibody therapeutic efforts. PubMed: 35136084DOI: 10.1038/s41467-022-28424-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4 Å) |
Structure validation
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