1v18
From Proteopedia
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THE CRYSTAL STRUCTURE OF BETA-CATENIN ARMADILLO REPEAT COMPLEXED WITH A PHOSPHORYLATED APC 20MER REPEAT.
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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:[175100], Desmoid disease, hereditary OMIM:[175100], Gardner syndrome OMIM:[175100], Gastric cancer OMIM:[175100], Turcot syndrome OMIM:[175100]
About this Structure
1V18 is a Protein complex structure of sequences from Homo sapiens and Mus musculus. 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 19:40:47 2007
