5T7Q

TIRAP phosphoinositide-binding motif

5T7Q の概要

• エントリーDOI: 10.2210/pdb5t7q/pdb
• NMR情報: BMRB: 30170
• 分子名称: Toll/interleukin-1 receptor domain-containing adapter protein (1 entity in total)
• 機能のキーワード: tirap, phosphoinositide, phosphorylation, phosphoinositide-binding motif; structure, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2550.20

構造登録者

Capelluto, D.G.S.,Ellena, J.F.,Armstrong, G.,Zhao, X.,Xiao, S. (登録日: 2016-09-05, 公開日: 2017-03-08, 最終更新日: 2024-05-15)

主引用文献

Zhao, X.,Xiong, W.,Xiao, S.,Tang, T.X.,Ellena, J.F.,Armstrong, G.S.,Finkielstein, C.V.,Capelluto, D.G.
Membrane targeting of TIRAP is negatively regulated by phosphorylation in its phosphoinositide-binding motif.
Sci Rep, 7:43043-43043, 2017

PubMed Abstract: Pathogen-activated Toll-like receptors (TLRs), such as TLR2 and TLR4, dimerize and move laterally across the plasma membrane to phosphatidylinositol (4,5)-bisphosphate-enriched domains. At these sites, TLRs interact with the TIR domain-containing adaptor protein (TIRAP), triggering a signaling cascade that leads to innate immune responses. Membrane recruitment of TIRAP is mediated by its phosphoinositide (PI)-binding motif (PBM). We show that TIRAP PBM transitions from a disordered to a helical conformation in the presence of either zwitterionic micelles or monodispersed PIs. TIRAP PBM bound PIs through basic and nonpolar residues with high affinity, favoring a more ordered structure. TIRAP is phosphorylated at Thr28 within its PBM, which leads to its ubiquitination and degradation. We demonstrate that phosphorylation distorts the helical structure of TIRAP PBM, reducing PI interactions and cell membrane targeting. Our study provides the basis for TIRAP membrane insertion and the mechanism by which it is removed from membranes to avoid sustained innate immune responses.

PubMed: 28225045
DOI: 10.1038/srep43043

実験手法

SOLUTION NMR