2GL7: Crystal Structure Of A Beta-CateninBCL9TCF4 COMPLEX

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.
PDB ID: 2GL7Download
MMDB ID: 42210
PDB Deposition Date: 2006/4/4
Updated in MMDB: 2006/11
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 2GL7: trimeric; determined by author and by software (PISA)
Molecular Components in 2GL7
Label Count Molecule
Proteins (3 molecules)
Beta-catenin(Gene symbol: CTNNB1)
Molecule annotation
Transcription Factor 7-like 2(Gene symbol: TCF7L2)
Molecule annotation
B-cell Lymphoma 9 Protein(Gene symbol: BCL9)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB