Crystal structure of a beta-catenin/Tcf complex.
The Wnt signaling pathway plays critical roles in embryonic development and tumorigenesis. Stimulation of the Wnt pathway results in the accumulation of a nuclear beta-catenin/Tcf complex, activating Wnt target genes. A crystal structure of beta-catenin bound to the beta-catenin binding domain of Tcf3 (Tcf3-CBD) has been determined. The Tcf3-CBD forms an elongated structure with three binding modules that runs antiparallel to beta-catenin along the positively charged groove formed by the armadillo repeats. Structure-based mutagenesis defines three sites in beta-catenin that are critical for binding the Tcf3-CBD and are differentially involved in binding APC, cadherin, and Axin. The structural and mutagenesis data reveal a potential target for molecular drug design studies.
Graham
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Department of Biological Structure University of Washington 98195, Seattle, WA, USA.
Weaver
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Mao
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Kimelman
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Xu
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D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D060466:Axin Protein; D015820:Cadherins / Q000378:metabolism; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024002:HMGB Proteins; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin
D060466:Axin Protein; C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D024002:HMGB Proteins; D011506:Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D029867:Xenopus Proteins; C555454:axin1 protein, Xenopus; D051176:beta Catenin