Structural basis of coactivation of liver receptor homolog-1 by ?-catenin.
We report the three-dimensional structure of a ?-catenin armadillo repeat in complex with the liver receptor homolog-1 (LRH-1) ligand binding domain at 2.8 A resolution as the first structure of ?-catenin in complex with any nuclear receptor. The surface of ?-catenin that binds LRH-1 partly overlaps defined contact sites for peptide ... segments of ?-catenin partners, including T-cell factor-4. The surface of LRH-1 that engages ?-catenin is comprised of helices 1, 9, and 10 and is distinct from known interaction surfaces of LRH-1, including corepressor and coactivator binding sites. Targeted mutagenesis of amino acids forming both sides of the LRH-1/?-catenin interface reveals that they are essential for stable interactions between these proteins in solution. The LRH-1 binding site in ?-catenin is also required for association with androgen receptor, providing evidence that the observed LRH-1/?-catenin interaction may be prototypic.
Mesh Terms:
DNA Mutational Analysis, Enzyme Assays, Humans, Luciferases, Models, Molecular, Point Mutation, Protein Binding, Protein Structure, Tertiary, Receptors, Androgen, Receptors, Cytoplasmic and Nuclear, Structure-Activity Relationship, beta Catenin
DNA Mutational Analysis, Enzyme Assays, Humans, Luciferases, Models, Molecular, Point Mutation, Protein Binding, Protein Structure, Tertiary, Receptors, Androgen, Receptors, Cytoplasmic and Nuclear, Structure-Activity Relationship, beta Catenin
Proc Natl Acad Sci U S A
Date: Jan. 03, 2012
PubMed ID: 22187462
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