ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structural basis for a molecular allosteric control mechanism of cofactor binding to nuclear receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 84 citations in OpenAlex.
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- DNA induces non-canonical dimerization of the farnesoid X receptor.Nucleic acids research · 2026Article
- HDAC3-driven immunometabolic reprogramming in type 2 diabetes and its complications: from enzymatic deacetylation to non-enzymatic scaffolding.Frontiers in immunology · 2026Review
- Multicomplex Pharmacophore Modeling of Estrogen Receptors Suggests the Probable Repurposing of Procaterol as an Antiproliferative Agent Against Breast Cancer Cells.International journal of molecular sciences · 2026Article
- ESR1 Regulates Fecundity and Functions in Sheep Endometrial Stromal Cells.International journal of molecular sciences · 2025Article
- Impact of Dietary Probiotics on the Immune and Reproductive Physiology of Pubertal Male Japanese Quail (Coturnix coturnix japonica) Administered at the Onset of Pre-Puberty.Probiotics and antimicrobial proteins · 2025Article
- Asymmetric allostery in estrogen receptor-α homodimers drives responses to the ensemble of estrogens in the hormonal milieu.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- New High-Throughput Screen Discovers Novel Ligands of Full-Length Nuclear Receptor LRH-1.ACS chemical biology · 2023Article
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- Human Estrogen Receptor Alpha Antagonists, Part 3: 3-D Pharmacophore and 3-D QSAR Guided Brefeldin A Hit-to-Lead Optimization toward New Breast Cancer Suppressants.Molecules (Basel, Switzerland) · 2022Article
- Cooperativity as quantification and optimization paradigm for nuclear receptor modulators.Chemical science · 2022Article
- Proliferative and Apoptotic Pathways in the Testis of QuailAnimals : an open access journal from MDPI · 2021Article
- Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer.Nucleic acids research · 2020Article
- Keratin 86 is up-regulated in the uterus during implantation, induced by oestradiol.BMC developmental biology · 2020Article
- Estrogen Deficiency Potentiates Thioacetamide-Induced Hepatic Fibrosis in Sprague-Dawley Rats.International journal of molecular sciences · 2019Article
- Allosteric pathways in nuclear receptors - Potential targets for drug design.Pharmacology & therapeutics · 2018Review
- The quaternary architecture of RARβ-RXRα heterodimer facilitates domain-domain signal transmission.Nature communications · 2017Article
- Synergistic Regulation of Coregulator/Nuclear Receptor Interaction by Ligand and DNA.Structure (London, England : 1993) · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription regulation by steroid hormones, vitamin derivatives, and metabolites is mediated by nuclear receptors (NRs), which play an important role in ligand-dependent gene expression and human health. NRs function as homodimers or heterodimers and are involved in a combinatorial, coordinated and sequentially orchestrated exchange between coregulators (corepressors, coactivators). The architecture of DNA-bound functional dimers positions the coregulators proteins. We previously demonstrated that retinoic acid (RAR-RXR) and vitamin D3 receptors (VDR-RXR) heterodimers recruit only one coactivator molecule asymmetrically without steric hindrance for the binding of a second cofactor. We now address the problem of homodimers for which the presence of two identical targets enhances the functional importance of the mode of binding. Using structural and biophysical methods and RAR as a model, we could dissect the molecular mechanism of coactivator recruitment to homodimers. Our study reveals an allosteric mechanism whereby binding of a coactivator promotes formation of nonsymmetrical RAR homodimers with a 21 stoichiometry. Ligand conformation and the cofactor binding site of the unbound receptor are affected through the dimer interface. A similar control mechanism is observed with estrogen receptor (ER) thus validating the negative cooperativity model for an established functional homodimer. Correlation with published data on other NRs confirms the general character of this regulatory pathway.
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