1P22

Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity on the SCFbeta-TrCP1 ubiquitin ligase

1P22 の概要

• エントリーDOI: 10.2210/pdb1p22/pdb
• 分子名称: F-box/WD-repeat protein 1A, Skp1, Beta-catenin (3 entities in total)
• 機能のキーワード: ubiquitination, degradation, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q9Y297 P35222
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69195.61

構造登録者

Wu, G.,Xu, G.,Schulman, B.A.,Jeffrey, P.D.,Harper, J.W.,Pavletich, N.P. (登録日: 2003-04-14, 公開日: 2003-07-08, 最終更新日: 2024-10-30)

主引用文献

Wu, G.,Xu, G.,Schulman, B.A.,Jeffrey, P.D.,Harper, J.W.,Pavletich, N.P.
Structure of a beta-TrCP1-Skp1-beta-Catenin complex: destruction motif binding and lysine specificity of the SCFbeta-TrCP1 ubiquitin ligase
Mol.Cell, 11:1445-1456, 2003

PubMed Abstract: The SCF ubiquitin ligases catalyze protein ubiquitination in diverse cellular processes. SCFs bind substrates through the interchangeable F box protein subunit, with the >70 human F box proteins allowing the recognition of a wide range of substrates. The F box protein beta-TrCP1 recognizes the doubly phosphorylated DpSGphiXpS destruction motif, present in beta-catenin and IkappaB, and directs the SCF(beta-TrCP1) to ubiquitinate these proteins at specific lysines. The 3.0 A structure of a beta-TrCP1-Skp1-beta-catenin complex reveals the basis of substrate recognition by the beta-TrCP1 WD40 domain. The structure, together with the previous SCF(Skp2) structure, leads to the model of SCF catalyzing ubiquitination by increasing the effective concentration of the substrate lysine at the E2 active site. The model's prediction that the lysine-destruction motif spacing is a determinant of ubiquitination efficiency is confirmed by measuring ubiquitination rates of mutant beta-catenin peptides, solidifying the model and also providing a mechanistic basis for lysine selection.

PubMed: 12820959
DOI: 10.1016/S1097-2765(03)00234-X

実験手法

X-RAY DIFFRACTION (2.95 Å)