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7ugq

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

Structural highlights

7ugq is a 18 chain structure with sequence from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.4Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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 A and 3.4 A 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(iGL) and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24(iGL) 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(gp120) glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.

HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design.,Dam KA, Barnes CO, Gristick HB, Schoofs T, Gnanapragasam PNP, Nussenzweig MC, Bjorkman PJ Nat Commun. 2022 Oct 17;13(1):6123. doi: 10.1038/s41467-022-33860-2. PMID:36253376^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dam KA, Barnes CO, Gristick HB, Schoofs T, Gnanapragasam PNP, Nussenzweig MC, Bjorkman PJ. HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design. Nat Commun. 2022 Oct 17;13(1):6123. doi: 10.1038/s41467-022-33860-2. PMID:36253376 doi:http://dx.doi.org/10.1038/s41467-022-33860-2