7UGO

Cryo-EM structure of BG24 inferred germline Fabs with mature CDR3s and 10-1074 Fabs in complex with HIV-1 Env immunogen BG505-SOSIPv4.1-GT1

7UGO の概要

• エントリーDOI: 10.2210/pdb7ugo/pdb
• EMDBエントリー: 26492
• 分子名称: Envelope glycoprotein gp120, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (15 entities in total)
• 機能のキーワード: hiv-1 env, neutralizing antibody, cd4 binding site antibody, viral protein, germline, precursor, immunogen, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 372364.32

構造登録者

Dam, K.A.,Bjorkman, P.J. (登録日: 2022-03-25, 公開日: 2022-10-26, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4.1 Å)