1jpw

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Revision as of 15:36, 12 November 2007

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spinqualitylabelsall models 1jpw, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of a Human Tcf-4 / beta-Catenin Complex

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The multifunctional protein beta-catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where, it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef, family transcription factors. Mutations in APC or in beta-catenin are, estimated to trigger formation of over 90% of all colon cancers. In, colonic epithelia, these mutations produce elevated levels of, Tcf4-beta-catenin, which stimulates a transcriptional response that, initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4-beta-catenin interaction may be an attractive goal, for therapeutic intervention. Here we describe the crystal structure of a, human Tcf4-beta-catenin complex and compare it with recent structures of, beta-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian, E-cadherin. The structure reveals anticipated similarities with the, closely related XTcf3 complex but unexpectedly lacks one component, observed in the XTcf3 structure.

Disease

Known diseases associated with this structure: Colorectal cancer OMIM:[116806], Diabetes mellitus, type 2, susceptibility to OMIM:[602228], Hepatoblastoma OMIM:[116806], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806], Pitt-Hopkins syndrome OMIM:[602272]

About this Structure

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

Reference

Structure of a human Tcf4-beta-catenin complex., Poy F, Lepourcelet M, Shivdasani RA, Eck MJ, Nat Struct Biol. 2001 Dec;8(12):1053-7. PMID:11713476

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