Crystal Structure of a β-Catenin/Tcf Complex
CellPublished 1 December 2000Open access
Thomas A. Graham, Carole Weaver, Feng Mao, David Kimelman, Wenqing Xu
Citations401
SJR quartileQ1
SJR score22.61
SNIP7.62
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TL;DR
Structural and mutagenesis data reveal a potential target for molecular drug design studies and define three sites in beta-catenin that are critical for binding the Tcf3-CBD and are differentially involved in binding APC, cadherin, and Axin.
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.
Keywords
Biochemistry, Genetics and Molecular Biology
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