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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Cadherins, Crystallography, X-Ray, Cytoskeletal Proteins, HMGB Proteins, Humans, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Precipitin Tests, Protein Binding, Protein Conformation, Proteins, Repressor Proteins, Sequence Alignment, Signal Transduction, TCF Transcription Factors, Trans-Activators, Transcription Factors, Xenopus, Xenopus Proteins, beta Catenin
Amino Acid Motifs, Amino Acid Sequence, Animals, Cadherins, Crystallography, X-Ray, Cytoskeletal Proteins, HMGB Proteins, Humans, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Precipitin Tests, Protein Binding, Protein Conformation, Proteins, Repressor Proteins, Sequence Alignment, Signal Transduction, TCF Transcription Factors, Trans-Activators, Transcription Factors, Xenopus, Xenopus Proteins, beta Catenin
Cell
Date: Dec. 08, 2000
PubMed ID: 11136974
View in: Pubmed Google Scholar
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