Abstract
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
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Animals
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Binding Sites
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Cadherins / chemistry
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Cadherins / metabolism
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Cell Line
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Crystallography, X-Ray
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Cytoskeletal Proteins / antagonists & inhibitors
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Cytoskeletal Proteins / chemistry*
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Cytoskeletal Proteins / metabolism*
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Drug Design
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Genes, Reporter / genetics
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HMGB Proteins*
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Humans
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Hydrogen Bonding
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Models, Molecular
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Protein Binding
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Protein Conformation
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Repetitive Sequences, Amino Acid
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Static Electricity
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TCF Transcription Factors
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Trans-Activators*
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Transcription Factor 7-Like 1 Protein
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transfection
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Xenopus Proteins / chemistry
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Xenopus Proteins / metabolism
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beta Catenin
Substances
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CTNNB1 protein, human
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Cadherins
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Cytoskeletal Proteins
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HMGB Proteins
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TCF Transcription Factors
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TCF7L1 protein, human
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TCF7L2 protein, human
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Trans-Activators
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Transcription Factor 7-Like 1 Protein
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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Xenopus Proteins
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beta Catenin
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tcf7l2 protein, Xenopus