3OUW

Structure of beta-catenin with Lef-1

Summary for 3OUW

• Entry DOI: 10.2210/pdb3ouw/pdb
• Related: 3OUX
• Descriptor: Catenin beta-1, Lymphoid enhancer-binding factor 1 (2 entities in total)
• Functional Keywords: wnt/beta-catenin signaling pathway, tcf, lef, transcription factors, phosphorylation, protein binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm: Q02248; Nucleus: P27782
• Total number of polymer chains: 2
• Total formula weight: 65820.70

Authors

Weis, W.I.,Sun, J. (deposition date: 2010-09-15, release date: 2010-11-24, Last modification date: 2024-10-09)

Primary citation

Sun, J.,Weis, W.I.
Biochemical and structural characterization of beta-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
J.Mol.Biol., 405:519-530, 2011

PubMed Abstract: In the Wnt/β-catenin signaling pathway, β-catenin activates target genes through its interactions with the T-cell factor/lymphoid enhancer-binding factor (TCF/Lef) family of transcription factors. The crystal structures of complexes between the β-catenin armadillo domain and the Lef-1 N-terminal domain show that the overall conformation and many of the interactions are similar to other published structures of TCFs bound to β-catenin. However, a second salt bridge in other TCF-β-catenin structures is absent in the structure of β-catenin-Lef-1 complex, indicating that this feature is not obligatory for β-catenin binding. Casein kinase II (CK2) has been shown to act as a positive regulator of Wnt signaling, and Lef-1 is a substrate of CK2. In vitro phosphorylation of purified Lef-1 was used to examine the effect of CK2 on the interaction of Lef-1 with β-catenin. Mass spectrometry data show that CK2 phosphorylation of Lef-1 N-terminal domain results in a single phosphorylation site at Ser40. Isothermal titration calorimetry revealed that β-catenin binds to nonphosphorylated or CK2-phosphorylated Lef-1 with the same affinity, which is consistent with the absence of phospho-Ser40 interactions in the crystal structure of phosphorylated Lef-1 N-terminal domain bound to β-catenin. These data indicate that the effect of CK2 on the Wnt/β-catenin pathway does not appear to be at the level of the Lef-1-β-catenin interaction.

PubMed: 21075118
DOI: 10.1016/j.jmb.2010.11.010

Experimental method

X-RAY DIFFRACTION (2.91 Å)