title: Structural basis of coactivation of liver receptor homolog-1 by β-catenin.
abstract: We report the three-dimensional structure of a β-catenin armadillo repeat in complex with the liver receptor homolog-1 (LRH-1) ligand binding domain at 2.8 Å resolution as the first structure of β-catenin in complex with any nuclear receptor. The surface of β-catenin that binds LRH-1 partly overlaps defined contact sites for peptide segments of β-catenin partners, including T-cell factor-4. The surface of LRH-1 that engages β-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/β-catenin interface reveals that they are essential for stable interactions between these proteins in solution. The LRH-1 binding site in β-catenin is also required for association with androgen receptor, providing evidence that the observed LRH-1/β-catenin interaction may be prototypic.
authors.affiliation: Department of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yumoto
authors.forename: Phuong
authors.initials: P
authors.lastname: Nguyen
authors.forename: Elena P
authors.initials: EP
authors.lastname: Sablin
authors.forename: John D
authors.initials: JD
authors.lastname: Baxter
authors.forename: Paul
authors.initials: P
authors.lastname: Webb
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fletterick
mesh_terms: D004252:DNA Mutational Analysis; D057075:Enzyme Assays; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008958:Models, Molecular; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D051176:beta Catenin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C082631:NR5A2 protein, human; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D051176:beta Catenin; D008156:Luciferases