6V8Z

VRC03 and 10-1074 Bound BG505 F14 HIV-1 SOSIP Envelope Trimer Structure

6V8Z の概要

• エントリーDOI: 10.2210/pdb6v8z/pdb
• EMDBエントリー: 21111 21112
• 分子名称: Envelope glycoprotein gp120, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: trimer, complex, immunogen, hiv-1, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 522124.36

構造登録者

Henderson, R.,Acharya, P. (登録日: 2019-12-12, 公開日: 2020-02-05, 最終更新日: 2024-10-16)

主引用文献

Henderson, R.,Lu, M.,Zhou, Y.,Mu, Z.,Parks, R.,Han, Q.,Hsu, A.L.,Carter, E.,Blanchard, S.C.,Edwards, R.J.,Wiehe, K.,Saunders, K.O.,Borgnia, M.J.,Bartesaghi, A.,Mothes, W.,Haynes, B.F.,Acharya, P.,Munir Alam, S.
Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.
Nat Commun, 11:520-520, 2020

PubMed Abstract: The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to prevent CD4-induced rearrangements in the HIV-1 BG505 Env trimer. Binding analysis and single-molecule Förster Resonance Energy Transfer confirm that these mutations prevent CD4-induced transitions of the HIV-1 Env. Structural analysis by single-particle cryo-electron microscopy performed on the BG505 SOSIP mutant Env proteins shows rearrangements in the gp120 topological layer contacts with gp41. Displacement of a conserved tryptophan (W571) from its typical pocket in these Env mutants renders the Env insensitive to CD4 binding. These results reveal the critical function of W571 as a conformational switch in Env allostery and receptor-mediated viral entry and provide insights on Env conformation that are relevant for vaccine design.

PubMed: 31980614
DOI: 10.1038/s41467-019-14196-w

実験手法

ELECTRON MICROSCOPY (2.9 Å)