Structure of a human Tcf4-beta-catenin complex.
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.
Pubmed ID: 11713476 RIS Download
Animals | Binding Sites | Cadherins | Cell Line | Crystallography, X-Ray | Cytoskeletal Proteins | Drug Design | Genes, Reporter | HMGB Proteins | Humans | Hydrogen Bonding | Models, Molecular | Protein Binding | Protein Conformation | Repetitive Sequences, Amino Acid | Static Electricity | TCF Transcription Factors | Trans-Activators | Transcription Factor 7-Like 1 Protein | Transcription Factor 7-Like 2 Protein | Transcription Factors | Transfection | Xenopus Proteins | beta Catenin