期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：1
页码：143-148
DOI：10.1073/pnas.1117036108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We report the three-dimensional structure of a {beta}-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 {beta}-catenin in complex with any nuclear receptor. The surface of {beta}-catenin that binds LRH-1 partly overlaps defined contact sites for peptide segments of {beta}-catenin partners, including T-cell factor-4. The surface of LRH-1 that engages {beta}-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/{beta}-catenin interface reveals that they are essential for stable interactions between these proteins in solution. The LRH-1 binding site in {beta}-catenin is also required for association with androgen receptor, providing evidence that the observed LRH-1/{beta}-catenin interaction may be prototypic.
