1luj
From Proteopedia
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Crystal Structure of the Beta-catenin/ICAT Complex
Contents |
Overview
Beta-catenin is a multifunctional protein involved in both cell adhesion, and transcriptional activation. Transcription mediated by the, beta-catenin/Tcf complex is involved in embryological development and is, upregulated in various cancers. We have determined the crystal structure, at 2.5 A resolution of a complex between beta-catenin and ICAT, a protein, that prevents the interaction between beta-catenin and Tcf/Lef family, transcription factors. ICAT contains a 3-helix bundle that binds armadillo, repeats 10-12 and a C-terminal tail that, similar to Tcf and E-cadherin, binds in the groove formed by armadillo repeats 5-9 of beta-catenin. We, show that ICAT selectively inhibits beta-catenin/Tcf binding in vivo, without disrupting beta-catenin/cadherin interactions. Thus, it should be, possible to design cancer therapeutics that inhibit beta-catenin-mediated, transcriptional activation without interfering with cell adhesion.
Disease
Known diseases associated with this structure: Colorectal cancer OMIM:[116806], Hepatoblastoma OMIM:[116806], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806]
About this Structure
1LUJ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT., Graham TA, Clements WK, Kimelman D, Xu W, Mol Cell. 2002 Sep;10(3):563-71. PMID:12408824
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