9BF6

Cryo-EM structure of the HIV-1 WITO IDL Env trimer in complex with PGT122 Fab

9BF6 の概要

• エントリーDOI: 10.2210/pdb9bf6/pdb
• EMDBエントリー: 44482 44484 44491
• 分子名称: Envelope glycoprotein gp41, Envelope glycoprotein gp120, PGT122 heavy chain, ... (9 entities in total)
• 機能のキーワード: cd4, hiv-1, sosip, vaccine, gp120, gp41, 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: 12
• 化学式量合計: 318185.17

構造登録者

Gorman, J.,Kwong, P.D. (登録日: 2024-04-16, 公開日: 2024-07-31, 最終更新日: 2024-10-23)

主引用文献

Zhang, P.,Gorman, J.,Tsybovsky, Y.,Lu, M.,Liu, Q.,Gopan, V.,Singh, M.,Lin, Y.,Miao, H.,Seo, Y.,Kwon, A.,Olia, A.S.,Chuang, G.Y.,Geng, H.,Lai, Y.T.,Zhou, T.,Mascola, J.R.,Mothes, W.,Kwong, P.D.,Lusso, P.
Design of soluble HIV-1 envelope trimers free of covalent gp120-gp41 bonds with prevalent native-like conformation.
Cell Rep, 43:114518-114518, 2024

PubMed Abstract: Soluble HIV-1 envelope (Env) trimers may serve as effective vaccine immunogens. The widely utilized SOSIP trimers have been paramount for structural studies, but the disulfide bond they feature between gp120 and gp41 constrains intersubunit mobility and may alter antigenicity. Here, we report an alternative strategy to generate stabilized soluble Env trimers free of covalent gp120-gp41 bonds. Stabilization was achieved by introducing an intrasubunit disulfide bond between the inner and outer domains of gp120, defined as interdomain lock (IDL). Correctly folded IDL trimers displaying a native-like antigenic profile were produced for HIV-1 Envs of different clades. Importantly, the IDL design abrogated CD4 binding while not affecting recognition by potent neutralizing antibodies to the CD4-binding site. By cryoelectron microscopy, IDL trimers were shown to adopt a closed prefusion configuration, while single-molecule fluorescence resonance energy transfer documented a high prevalence of native-like conformation. Thus, IDL trimers may be promising candidates as vaccine immunogens.

PubMed: 39028623
DOI: 10.1016/j.celrep.2024.114518

実験手法

ELECTRON MICROSCOPY (4.5 Å)