Crystal structure of a beta-catenin/Tcf complex.
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Graham TA, Weaver C, Mao F, Kimelman D, Xu W
Crystal structure of a beta-catenin/Tcf complex.
Cell. 2000 Dec 8;103(6):885-96.
- PubMed ID
- 11136974 [ View in PubMed]
- Abstract
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.