7UGM

Crystal Structure of BG24-iGL CDR3mat Fab

Summary for 7UGM

• Entry DOI: 10.2210/pdb7ugm/pdb
• Descriptor: BG24-iGL CDR3mat Fab heavy chain, BG24-iGL CDR3mat Fab light chain (3 entities in total)
• Functional Keywords: fab, igg, bg24, anti-hiv antibody, bnab, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 46195.43

Authors

Dam, K.A.,Barnes, C.O.,Bjorkman, P.J. (deposition date: 2022-03-25, release date: 2022-11-09, Last modification date: 2024-11-06)

Primary citation

Dam, K.A.,Barnes, C.O.,Gristick, H.B.,Schoofs, T.,Gnanapragasam, P.N.P.,Nussenzweig, M.C.,Bjorkman, P.J.
HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design.
Nat Commun, 13:6123-6123, 2022

PubMed Abstract: BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24 and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24 variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276 glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.

PubMed: 36253376
DOI: 10.1038/s41467-022-33860-2

Experimental method

X-RAY DIFFRACTION (1.4 Å)