2gl7
From Proteopedia
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| , resolution 2.60Å | |||||||
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| Gene: | CTNNB1, CTNNB (Homo sapiens), TCF7L2, TCF4 (Homo sapiens), BCL9 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of a beta-catenin/BCL9/Tcf4 complex
Contents |
Overview
The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A 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.
Disease
Known diseases associated with this structure: Colorectal cancer OMIM:[116806], Diabetes mellitus, type 2, susceptibility to OMIM:[602228], Hepatoblastoma OMIM:[116806], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806], Pitt-Hopkins syndrome OMIM:[602272]
About this Structure
2GL7 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of a beta-catenin/BCL9/Tcf4 complex., Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W, Mol Cell. 2006 Oct 20;24(2):293-300. PMID:17052462
Page seeded by OCA on Thu Mar 20 17:05:58 2008
