1T08

Crystal structure of beta-catenin/ICAT helical domain/unphosphorylated APC R3

1T08 の概要

• エントリーDOI: 10.2210/pdb1t08/pdb
• 分子名称: Beta-catenin, Beta-catenin-interacting protein 1, Adenomatous polyposis coli protein, ... (4 entities in total)
• 機能のキーワード: beta-catenin; wnt signal; apc; 20mer repeat; wnt signaling, cell adhesion-cell cycle complex, cell adhesion/cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P35222; Cytoplasm (By similarity): Q9NSA3; Cell junction, adherens junction: P25054
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 63456.42

構造登録者

Ha, N.-C.,Tonozuka, T.,Stamos, J.L.,Weis, W.I. (登録日: 2004-04-07, 公開日: 2004-10-12, 最終更新日: 2023-08-23)

主引用文献

Ha, N.-C.,Tonozuka, T.,Stamos, J.L.,Choi, H.J.,Weis, W.I.
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation
Mol.Cell, 15:511-521, 2004

PubMed Abstract: The transcriptional coactivator beta-catenin mediates Wnt growth factor signaling. In the absence of a Wnt signal, casein kinase 1 (CK1) and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate cytosolic beta-catenin, thereby flagging it for recognition and destruction by the ubiquitin/proteosome machinery. Phosphorylation occurs in a multiprotein complex that includes the kinases, beta-catenin, axin, and the Adenomatous Polyposis Coli (APC) protein. The role of APC in this process is poorly understood. CK1epsilon and GSK-3beta phosphorylate APC, which increases its affinity for beta-catenin. Crystal structures of phosphorylated and nonphosphorylated APC bound to beta-catenin reveal a phosphorylation-dependent binding motif generated by mutual priming of CK1 and GSK-3beta substrate sequences. Axin is shown to act as a scaffold for substrate phosphorylation by these kinases. Phosphorylated APC and axin bind to the same surface of, and compete directly for, beta-catenin. The structural and biochemical data suggest a novel model for how APC functions in beta-catenin degradation.

PubMed: 15327768
DOI: 10.1016/j.molcel.2004.08.010

実験手法

X-RAY DIFFRACTION (2.1 Å)