7TFO

Cryo-EM structure of HIV-1 Env trimer BG505 SOSIP.664 in complex with CD4bs antibody Ab1573

This is a non-PDB format compatible entry.

Summary for 7TFO

• Entry DOI: 10.2210/pdb7tfo/pdb
• Related: 7TFN
• EMDB information: 25877 25878
• Descriptor: Envelope glycoprotein BG505 SOSIP.664 - gp120, CD4 binding site antibody Ab1573 - Fab heavy chain, CD4 binding site antibody Ab1573 - Fab light chain, ... (8 entities in total)
• Functional Keywords: cryo-em structure of the trimeric hiv-1 env ecto-domain bg505 sosip.664 in complex with cd4 binding site antibody ab1573, 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: 359633.46

Authors

Yang, Z.,Bjorkman, P.J. (deposition date: 2022-01-06, release date: 2022-01-26, Last modification date: 2024-10-16)

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

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: 35136084
DOI: 10.1038/s41467-022-28424-3

Experimental method

ELECTRON MICROSCOPY (4.1 Å)