2NAE

Membrane-bound mouse CD28 cytoplasmic tail

2NAE の概要

• エントリーDOI: 10.2210/pdb2nae/pdb
• NMR情報: BMRB: 25935
• 分子名称: T-cell-specific surface glycoprotein CD28 (1 entity in total)
• 機能のキーワード: cd28, membrane bound protein, bicelle, costimulation, tcr, signaling protein
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P31041
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5093.79

構造登録者

Li, H.,Xu, C.,Pan, W. (登録日: 2015-12-23, 公開日: 2016-12-21, 最終更新日: 2024-05-15)

主引用文献

Yang, W.,Pan, W.,Chen, S.,Trendel, N.,Jiang, S.,Xiao, F.,Xue, M.,Wu, W.,Peng, Z.,Li, X.,Ji, H.,Liu, X.,Jiang, H.,Wang, H.,Shen, H.,Dushek, O.,Li, H.,Xu, C.
Dynamic regulation of CD28 conformation and signaling by charged lipids and ions.
Nat.Struct.Mol.Biol., 24:1081-1092, 2017

PubMed Abstract: CD28 provides an essential costimulatory signal for T cell activation, and its function is critical in antitumor immunity. However, the molecular mechanism of CD28 transmembrane signaling remains elusive. Here we show that the conformation and signaling of CD28 are regulated by two counteractive charged factors, acidic phospholipids and Ca ions. NMR spectroscopy analyses showed that acidic phospholipids can sequester CD28 signaling motifs within the membrane, thereby limiting CD28 basal signaling. T cell receptor (TCR) activation induced an increase in the local Ca concentration around CD28, and Ca directly disrupted CD28-lipid interaction, leading to opening and signaling of CD28. We observed that the TCR, Ca, and CD28 together form a dual-positive-feedback circuit that substantially amplifies T cell signaling and thus increases antigen sensitivity. This work unravels a new regulatory mechanism for CD28 signaling and thus contributes to the understanding of the dependence of costimulation signaling on TCR signaling and the high sensitivity of T cells.

PubMed: 29058713
DOI: 10.1038/nsmb.3489

実験手法

SOLUTION NMR