2N2N

Tom1 negatively modulates binding of Tollip to phosphatidylinositol 3-phosphate via a coupled folding and binding mechanism

2N2N の概要

• エントリーDOI: 10.2210/pdb2n2n/pdb
• NMR情報: BMRB: 25602
• 分子名称: Target of Myb protein 1 (1 entity in total)
• 機能のキーワード: protein transport
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : O60784
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11501.09

構造登録者

Xiao, S.,Armstrong, G.,Capelluto, D. (登録日: 2015-05-11, 公開日: 2015-09-16, 最終更新日: 2024-05-15)

主引用文献

Xiao, S.,Brannon, M.K.,Zhao, X.,Fread, K.I.,Ellena, J.F.,Bushweller, J.H.,Finkielstein, C.V.,Armstrong, G.S.,Capelluto, D.G.
Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism.
Structure, 23:1910-1920, 2015

PubMed Abstract: Early endosomes represent the first sorting station for vesicular ubiquitylated cargo. Tollip, through its C2 domain, associates with endosomal phosphatidylinositol 3-phosphate (PtdIns(3)P) and binds ubiquitylated cargo in these compartments via its C2 and CUE domains. Tom1, through its GAT domain, is recruited to endosomes by binding to the Tollip Tom1-binding domain (TBD) through an unknown mechanism. Nuclear magnetic resonance data revealed that Tollip TBD is a natively unfolded domain that partially folds at its N terminus when bound to Tom1 GAT through high-affinity hydrophobic contacts. Furthermore, this association abrogates binding of Tollip to PtdIns(3)P by additionally targeting its C2 domain. Tom1 GAT is also able to bind ubiquitin and PtdIns(3)P at overlapping sites, albeit with modest affinity. We propose that association with Tom1 favors the release of Tollip from endosomal membranes, allowing Tollip to commit to cargo trafficking.

PubMed: 26320582
DOI: 10.1016/j.str.2015.07.017

実験手法

SOLUTION NMR