Structural basis of coactivation of liver receptor homolog-1 by β-catenin
Open accessAbstract
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.
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Predictive modeling suggests that β-catenin interacts with the AR hormone binding domain on a surface that overlaps with BF3.
“Predictive modeling suggests that β-catenin interacts with the AR hormone binding domain on a surface that overlaps with BF3.”
From The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling (2015) · cites this paper as [25]
The Results report that β-catenin interacts with the AR ligand-binding domain, and the Discussion links AR binding to a region of β-catenin also used by LRH-1. Neither section reports predictive modeling that places the contact on an AR surface overlapping BF3; the Discussion says the AR binding interface remains uncertain. The indexed passages provide no page numbers. (LLM, conf=0.84)
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Self-citation
- Authors
- Yumoto, F., Nguyen, P., Sablin, E. P., Baxter, J. D., Webb, P., & Fletterick, R. J.
- Affiliations
- University of California, San Francisco (US)
- Houston Methodist (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-12-20
- Volume
- 109
- Issue
- 1
- Pages
- 143-148
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3252924
- OpenAlex
- W2054093429
- Cited by
- 63
- References
- 65
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 8 · 2014: 4 · 2013: 9 · 2012: 4
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 41482, DK51281, R01DK078075, R21DK084504, R01DK051281)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- β-catenin, LRH-1, armadillo repeats, protein-protein interaction, ligand-binding domain, T-cell factor 4, androgen receptor, transcriptional coactivator, protein complex structure
- MeSH terms
- DNA Mutational Analysis, Humans, Luciferases, Models, Molecular, Protein Binding, Receptors, Androgen, Structure-Activity Relationship, Point Mutation, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, beta Catenin, Enzyme Assays
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