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.
Mesh Terms:
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 Factors, Transfection, Xenopus Proteins, beta Catenin
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 Factors, Transfection, Xenopus Proteins, beta Catenin
Nat. Struct. Biol.
Date: Dec. 01, 2001
PubMed ID: 11713476
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