8TGW

Cryo-EM structure of 1059 SOSIP trimer purified via Galanthus nivalis lectin chromatography

8TGW の概要

• エントリーDOI: 10.2210/pdb8tgw/pdb
• EMDBエントリー: 41246
• 分子名称: 1059 SOSIP Surface protein gp120, 1059 SOSIP Transmembrane protein gp41, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: hiv-1, glycoprotein, lectin, trimer, viral protein
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 242491.96

構造登録者

Parsons, R.J.,Pothula, K.,Acharya, P. (登録日: 2023-07-13, 公開日: 2024-08-28, 最終更新日: 2024-10-09)

主引用文献

Parthasarathy, D.,Pothula, K.R.,Ratnapriya, S.,Cervera Benet, H.,Parsons, R.,Huang, X.,Sammour, S.,Janowska, K.,Harris, M.,Sodroski, J.,Acharya, P.,Herschhorn, A.
Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies.
Nat Commun, 15:7334-7334, 2024

PubMed Abstract: HIV-1 envelope glycoproteins (Envs) of most primary HIV-1 strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims to mimic the closed Env conformation as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely closed Env conformations of 6 out of 13 transmitted/founder (T/F) strains that are sensitive to antibodies that recognize internal epitopes typically exposed on open Envs. A 3.6 Å cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) reveals protomer motion that increased sampling of states with incompletely closed trimer apex. We reconstruct de novo the post-transmission evolutionary pathway of a second T/F. Evolved viruses exhibit increased Env resistance to cold, soluble CD4 and 19b, all of which correlate with closing of the adapted Env trimer. Lastly, we show that the ultra-broad N6 bnAb efficiently recognizes different Env conformations and exhibits improved antiviral breadth against VRC01-resistant Envs isolated during the first-in-humans antibody-mediated-prevention trial.

PubMed: 39187497
DOI: 10.1038/s41467-024-51656-4

実験手法

ELECTRON MICROSCOPY (3.6 Å)