1th1

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spinqualitylabelsall models 1th1, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Adenoma, periampullary OMIM:[175100], Adenomatous polyposis coli OMIM:[175100], Adenomatous polyposis coli, attenuated OMIM:[175100], Colorectal cancer OMIM:[116806], Colorectal cancer OMIM:[175100], Desmoid disease, hereditary OMIM:[175100], Gardner syndrome OMIM:[175100], Gastric cancer OMIM:[175100], Hepatoblastoma OMIM:[116806], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806], Turcot syndrome OMIM:[175100]

About this Structure

1TH1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function., Xing Y, Clements WK, Le Trong I, Hinds TR, Stenkamp R, Kimelman D, Xu W, Mol Cell. 2004 Aug 27;15(4):523-33. PMID:15327769

Page seeded by OCA on Mon Nov 12 19:24:55 2007