Crystal Structure of a β-Catenin/Tcf Complex

phosphorylated b-catenin and targets it for degradation The Wnt signaling pathway plays critical roles in emby the proteosome. Active Wnt signaling inhibits the bryonic development and tumorigenesis. Stimulation phosphorylation of b-catenin by GSK-3b by a mostly of the Wnt pathway results in the accumulation of a unknown mechanism, thus preventing the degradation nuclear b-catenin/Tcf complex, activating Wnt target of b-catenin. genes. A crystal structure of b-catenin bound to the Tcf/LEF-1 family members, Axin, APC, and the cadb-catenin binding domain of Tcf3 (Tcf3-CBD) has been herins bind b-catenin in the large central core of the determined. The Tcf3-CBD forms an elongated strucprotein, which contains 12 armadillo repeats. The preture with three binding modules that runs antiparallel viously reported crystal structure of the armadillo repeat to b-catenin along the positively charged groove region of murine b-catenin revealed that each repeat formed by the armadillo repeats. Structure-based muconsists of three a helices, and together the 12 repeats tagenesis defines three sites in b-catenin that are critiform a superhelix that features a long positively charged cal for binding the Tcf3-CBD and are differentially groove (Huber et al., 1997). While the b-catenin binding involved in binding APC, cadherin, and Axin. The strucdomain (CBD) of the different b-catenin partners has tural and mutagenesis data reveal a potential target been well defined in several cases (Hulsken et al., 1994; for molecular drug design studies. Rubinfeld et al., 1995; Behrens et al., 1996; Molenaar et