This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1t08
From Proteopedia
|
Crystal structure of beta-catenin/ICAT helical domain/unphosphorylated APC R3
Contents |
Overview
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.
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
1T08 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation., Ha NC, Tonozuka T, Stamos JL, Choi HJ, Weis WI, Mol Cell. 2004 Aug 27;15(4):511-21. PMID:15327768
Page seeded by OCA on Mon Nov 12 19:18:37 2007
