7UGQ

Cryo-EM structure of BG24 Fabs with an inferred germline CDRL1 and 10-1074 Fabs in complex with HIV-1 Env 6405-SOSIP.664

Summary for 7UGQ

• Entry DOI: 10.2210/pdb7ugq/pdb
• EMDB information: 26496
• Descriptor: Envelope glycoprotein gp120, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• Functional Keywords: hiv-1 env, neutralizing antibody, cd4 binding site antibody, viral protein, germline, precursor, immunogen, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 18
• Total formula weight: 375086.36

Authors

Dam, K.A.,Bjorkman, P.J. (deposition date: 2022-03-25, release date: 2022-11-09, Last modification date: 2024-10-16)

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

ELECTRON MICROSCOPY (3.4 Å)