8FYJ

Structure of HIV-1 BG505 SOSIP-HT2 in complex with two CD4 molecules (class I)

8FYJ の概要

• エントリーDOI: 10.2210/pdb8fyj/pdb
• EMDBエントリー: 29580
• 分子名称: Envelope glycoprotein gp160, Envelope glycoprotein gp41, T-cell surface glycoprotein CD4, ... (9 entities in total)
• 機能のキーワード: viral protein, hiv-1, immune system, 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: 8
• 化学式量合計: 302539.53

構造登録者

Fan, C.,Dam, K.A.,Bjorkman, P.J. (登録日: 2023-01-26, 公開日: 2023-10-18, 最終更新日: 2024-11-20)

主引用文献

Dam, K.A.,Fan, C.,Yang, Z.,Bjorkman, P.J.
Intermediate conformations of CD4-bound HIV-1 Env heterotrimers.
Nature, 623:1017-1025, 2023

PubMed Abstract: HIV-1 envelope (Env) exhibits distinct conformational changes in response to host receptor (CD4) engagement. Env, a trimer of gp120 and gp41 heterodimers, has been structurally characterized in a closed, prefusion conformation with closely associated gp120s and coreceptor binding sites on gp120 V3 hidden by V1V2 loops and in fully saturated CD4-bound open Env conformations with changes including outwardly rotated gp120s and displaced V1V2 loops. To investigate changes resulting from substoichiometric CD4 binding, we solved single-particle cryo-electron microscopy (cryo-EM) structures of soluble, native-like heterotrimeric Envs bound to one or two CD4 molecules. Most of the Env trimers bound to one CD4 adopted the closed, prefusion Env state, with a minority exhibiting a heterogeneous partially open Env conformation. When bound to two CD4s, the CD4-bound gp120s exhibited an open Env conformation including a four-stranded gp120 bridging sheet and displaced gp120 V1V2 loops that expose the coreceptor sites on V3. The third gp120 adopted an intermediate, occluded-open state that showed gp120 outward rotation but maintained the prefusion three-stranded gp120 bridging sheet with only partial V1V2 displacement and V3 exposure. We conclude that most of the engagements with one CD4 molecule were insufficient to stimulate CD4-induced conformational changes, whereas binding two CD4 molecules led to Env opening in CD4-bound protomers only. The substoichiometric CD4-bound soluble Env heterotrimer structures resembled counterparts derived from a cryo-electron tomography study of complexes between virion-bound Envs and membrane-anchored CD4 (ref. ), validating their physiological relevance. Together, these results illuminate intermediate conformations of HIV-1 Env and illustrate its structural plasticity.

PubMed: 37993719
DOI: 10.1038/s41586-023-06639-8

実験手法

ELECTRON MICROSCOPY (4 Å)