Crystal structure of a β-catenin/BCL9/Tcf4 complex
Crystal structure of a β-catenin/BCL9/Tcf4 complex
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DOI：
10.1016/j.molcel.2006.09.001
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发表时间：
2006-10-20
期刊：
影响因子：
16
通讯作者：
Xu, Wenqing
中科院分区：
文献类型：
--
作者：
Sampietro, James;Dahlberg, Caroline L.;Xu, Wenqing
The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Writ pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Writ target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 angstrom resolution. Our studies reveal that the beta-catenin binding site of BCL9 is distinct from that of most other beta-catenin partners and forms a good target for developing drugs that block canonical Wnt/beta-catenin signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix that binds to the first armadillo repeat of beta-catenin, which can be mutated to prevent beta-catenin binding to BCL9 without affecting cadherin or alpha-catenin binding. We also demonstrate that beta-catenin Y142 phosphorylation, which has been proposed to regulate BCL9-2 binding, does not directly affect the interaction of beta-catenin with either BCL9 or BCL9-2.
