2GL7

Crystal Structure of a beta-catenin/BCL9/Tcf4 complex

Summary for 2GL7

• Entry DOI: 10.2210/pdb2gl7/pdb
• Descriptor: Beta-catenin, Transcription factor 7-like 2, B-cell lymphoma 9 protein, ... (4 entities in total)
• Functional Keywords: protein complex, armadillo repeat, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P35222; Nucleus, PML body: Q9NQB0; Nucleus (By similarity): O00512
• Total number of polymer chains: 6
• Total formula weight: 142318.44

Authors

Sampietro, J. (deposition date: 2006-04-04, release date: 2006-10-31, Last modification date: 2024-02-14)

Primary citation

Sampietro, J.,Dahlberg, C.L.,Cho, U.S.,Hinds, T.R.,Kimelman, D.,Xu, W.
Crystal Structure of a beta-Catenin/BCL9/Tcf4 Complex.
Mol.Cell, 24:293-300, 2006

PubMed Abstract: 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.

PubMed: 17052462
DOI: 10.1016/j.molcel.2006.09.001

Experimental method

X-RAY DIFFRACTION (2.6 Å)