PDBsum entry 2gl7

Transcription

PDB id: 2gl7

Contents

Protein chains

512 a.a.

30 a.a.

23 a.a.

28 a.a.

17 a.a.

Waters ×128

References listed in PDB file

Key reference

Title

Crystal structure of a beta-Catenin/bcl9/tcf4 complex.

Authors

J.Sampietro, C.L.Dahlberg, U.S.Cho, T.R.Hinds, D.Kimelman, W.Xu.

Ref.

Mol Cell, 2006, 24, 293-300. [DOI no: 10.1016/j.molcel.2006.09.001]

PubMed id

17052462

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.

Figure 3.
Figure 3. Point Mutations Diminish the Ability of hBcl9 to Bind to β-Catenin

Figure 4.
Figure 4. BCL9 and BCL9-2, but Not α-Catenin, Bind Equally Well to WT β-Catenin and Y142E β-Catenin

The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 24, 293-300) copyright 2006.