7SD3

Cytoplasmic tail deleted HIV-1 Env bound with three 4E10 Fabs

7SD3 の概要

• エントリーDOI: 10.2210/pdb7sd3/pdb
• EMDBエントリー: 25022 25024 25025 25045
• 分子名称: 4E10 Fab light chain, 4E10 Fab heavy chain, Envelope glycoprotein gp120, ... (7 entities in total)
• 機能のキーワード: hiv, envelope, spike, fab, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 376769.32

構造登録者

Yang, S.,Walz, T. (登録日: 2021-09-29, 公開日: 2022-11-09, 最終更新日: 2024-11-06)

主引用文献

Yang, S.,Hiotis, G.,Wang, Y.,Chen, J.,Wang, J.H.,Kim, M.,Reinherz, E.L.,Walz, T.
Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack.
Nat Commun, 13:6393-6393, 2022

PubMed Abstract: Vaccines targeting HIV-1's gp160 spike protein are stymied by high viral mutation rates and structural chicanery. gp160's membrane-proximal external region (MPER) is the target of naturally arising broadly neutralizing antibodies (bnAbs), yet MPER-based vaccines fail to generate bnAbs. Here, nanodisc-embedded spike protein was investigated by cryo-electron microscopy and molecular-dynamics simulations, revealing spontaneous ectodomain tilting that creates vulnerability for HIV-1. While each MPER protomer radiates centrally towards the three-fold axis contributing to a membrane-associated tripod structure that is occluded in the upright spike, tilting provides access to the opposing MPER. Structures of spike proteins with bound 4E10 bnAb Fabs reveal that the antibody binds exposed MPER, thereby altering MPER dynamics, modifying average ectodomain tilt, and imposing strain on the viral membrane and the spike's transmembrane segments, resulting in the abrogation of membrane fusion and informing future vaccine development.

PubMed: 36302771
DOI: 10.1038/s41467-022-34008-y

実験手法

ELECTRON MICROSCOPY (3.67 Å)