ArticleThe Journal of biological chemistry2018
Ligand binding and heterodimerization with retinoid X receptor α (RXRα) induce farnesoid X receptor (FXR) conformational changes affecting coactivator binding.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Bile acids as a "new hormone" in aging-related liver disease.Life medicine · 2026Review
- Microbiota-Derived Metabolites in the Epigenetic Regulation of Redox Homeostasis.Antioxidants (Basel, Switzerland) · 2026Review
- Gut microbiota dysbiosis induced by tibial dyschondroplasia in turn accelerates disease pathogenesis through the gut-bone axis in broilers.Poultry science · 2026Article
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- FXR in bone metabolism: An emerging regulator.iScience · 2026Review
- DNA induces non-canonical dimerization of the farnesoid X receptor.Nucleic acids research · 2026Article
- Structure-Based Discovery of Obeticholic Acid Derivatives as Novel Farnesoid X Receptor Partial Agonists with Improved Selectivity and Reduced Off-Target Effects.ChemMedChem · 2026Article
- Beyond vitamin D: integrating nuclear receptor signaling networks in periodontal health and disease.Frontiers in physiology · 2026Review
- FGF19 in Solid Tumors: Molecular Mechanisms, Metabolic Reprogramming, and Emerging Therapeutic Opportunities.Theranostics · 2026Review
- Review
- Hepatic protein kinase Cβ antagonizing p38American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
- Polymorphic Variants of Selected Genes Regulating Bile Acid Homeostasis in Women with Intrahepatic Cholestasis of Pregnancy.International journal of molecular sciences · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Geniposidic Acid Targeting FXR "S332 and H447" Mediated Conformational Change to Upregulate CYPs and miR-19a-3p to Ameliorate Drug-Induced Liver Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Structural basis for the asymmetric binding of coactivator SRC1 to FXR-RXRα and allosteric communication within the complex.Communications biology · 2025Article
- Simulations Reveal Unique Roles for the FXR Hinge in the FXR-RXR Nuclear Receptor Heterodimer.ACS bio & med chem Au · 2025Article
- Alternative splicing is an FXRα loss-of-function mechanism and impacts energy metabolism in hepatocarcinoma cells.The Journal of biological chemistry · 2025Article
- Automated design of multi-target ligands by generative deep learning.Nature communications · 2024Article
- Computational study of novel natural agonists targeting farnesoid X receptor.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear receptor farnesoid X receptor (FXR) functions as the major bile acid sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of dietary fats and vitamins. Because of its central role in metabolism, FXR represents an important drug target to manage metabolic and other diseases, such as primary biliary cirrhosis and nonalcoholic steatohepatitis. FXR and nuclear receptor retinoid X receptor α (RXRα) form a heterodimer that controls the expression of numerous downstream genes. To date, the structural basis and functional consequences of the FXR/RXR heterodimer interaction have remained unclear. Herein, we present the crystal structures of the heterodimeric complex formed between the ligand-binding domains of human FXR and RXRα. We show that both FXR and RXR bind to the transcriptional coregulator steroid receptor coactivator 1 with higher affinity when they are part of the heterodimer complex than when they are in their respective monomeric states. Furthermore, structural comparisons of the FXR/RXRα heterodimers and the FXR monomers bound with different ligands indicated that both heterodimerization and ligand binding induce conformational changes in the C terminus of helix 11 in FXR that affect the stability of the coactivator binding surface and the coactivator binding in FXR. In summary, our findings shed light on the allosteric signal transduction in the FXR/RXR heterodimer, which may be utilized for future drug development targeting FXR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.