Structural basis of coactivation of liver receptor homolog-1 by β-catenin

Fumiaki Yumoto, Phuong Nguyen, Elena P. Sablin, John D. Baxter, Paul Webb, Robert J. Fletterick

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)143-148
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - Jan 3 2012


  • Crystal structure
  • Crystallography
  • Protein-protein interaction

ASJC Scopus subject areas

  • General


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