7FJF

Cryo-EM structure of a membrane protein(CS)

7FJF の概要

• エントリーDOI: 10.2210/pdb7fjf/pdb
• EMDBエントリー: 31620
• 分子名称: T-cell surface glycoprotein CD3 zeta chain, T-cell surface glycoprotein CD3 delta chain, T-cell surface glycoprotein CD3 epsilon chain, ... (7 entities in total)
• 機能のキーワード: membrane, immune, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 189723.69

構造登録者

Chen, Y.,Zhu, Y.,Gao, W.,Zhang, A.,Guo, C.,Huang, Z. (登録日: 2021-08-03, 公開日: 2022-07-27, 最終更新日: 2024-10-09)

主引用文献

Chen, Y.,Zhu, Y.,Li, X.,Gao, W.,Zhen, Z.,Huang, B.,Ma, Z.,Zhang, A.,Song, X.,Ma, Y.,Guo, C.,Zhang, F.,Huang, Z.
Cholesterol inhibits TCR signaling by directly restricting TCR-CD3 core tunnel motility.
Mol.Cell, 82:1278-1287.e5, 2022

PubMed Abstract: Cholesterol molecules specifically bind to the resting αβTCR to inhibit cytoplasmic CD3ζ ITAM phosphorylation through sequestering the TCR-CD3 complex in an inactive conformation. The mechanisms of cholesterol-mediated inhibition of TCR-CD3 and its activation remain unclear. Here, we present cryoelectron microscopy structures of cholesterol- and cholesterol sulfate (CS)-inhibited TCR-CD3 complexes and an auto-active TCR-CD3 variant. The structures reveal that cholesterol molecules act like a latch to lock CD3ζ into an inactive conformation in the membrane. Mutations impairing binding of cholesterol molecules to the tunnel result in the movement of the proximal C terminus of the CD3ζ transmembrane helix, thereby activating the TCR-CD3 complex in human cells. Together, our data reveal the structural basis of TCR inhibition by cholesterol, illustrate how the cholesterol-binding tunnel is allosterically coupled to TCR triggering, and lay a foundation for the development of immunotherapies through directly targeting the TCR-CD3 complex.

PubMed: 35271814
DOI: 10.1016/j.molcel.2022.02.017

実験手法

ELECTRON MICROSCOPY (3.1 Å)