1TH1

Beta-catenin in complex with a phosphorylated APC 20aa repeat fragment

Summary for 1TH1

• Entry DOI: 10.2210/pdb1th1/pdb
• Descriptor: Beta-catenin, Adenomatous polyposis coli protein (3 entities in total)
• Functional Keywords: protein-protein complex, cell adhesion-antitumor protein complex, cell adhesion/antitumor protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P35222; Cell junction, adherens junction: P25054
• Total number of polymer chains: 4
• Total formula weight: 155244.70

Authors

Xing, Y.,Clements, W.K.,Le Trong, I.,Hinds, T.R.,Stenkamp, R.,Kimelman, D.,Xu, W. (deposition date: 2004-05-31, release date: 2004-09-07, Last modification date: 2024-10-30)

Primary citation

Xing, Y.,Clements, W.K.,Le Trong, I.,Hinds, T.R.,Stenkamp, R.,Kimelman, D.,Xu, W.
Crystal Structure of a beta-Catenin/APC Complex Reveals a Critical Role for APC Phosphorylation in APC Function.
Mol.Cell, 15:523-533, 2004

PubMed Abstract: The tumor suppressor adenomatous polyposis coli (APC) plays a critical role in the turnover of cytosolic beta-catenin, the key effector of the canonical Wnt signaling pathway. APC contains seven 20 amino acid (20 aa) beta-catenin binding repeats that are required for beta-catenin turnover. We have determined the crystal structure of beta-catenin in complex with a phosphorylated APC fragment containing two 20 aa repeats. Surprisingly, one single phosphorylated 20 aa repeat, together with its flanking regions, covers the entire structural groove of beta-catenin and may thus compete for beta-catenin binding with all other beta-catenin armadillo repeat partners. Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf. Our work suggests that the phosphorylation of the APC 20 aa repeats could be a critical switch for APC function.

PubMed: 15327769
DOI: 10.1016/j.molcel.2004.08.001

Experimental method

X-RAY DIFFRACTION (2.5 Å)