ArticleThe EMBO journal1997
A mutation mimicking ligand-induced conformational change yields a constitutive RXR that senses allosteric effects in heterodimers.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 136 citations in OpenAlex.
- Endocrine-disrupting chemicals as prostate carcinogens.Nature reviews. Urology · 2025Review
- Modulation of retinoid-X-receptors differentially regulates expression of apolipoprotein genes apoc1 and apoeb by zebrafish microglia.Biology open · 2022Article
- Regulation of RXR-RAR Heterodimers by RXR- and RAR-Specific Ligands and Their Combinations.Cells · 2019Article
- Overview of the structure-based non-genomic effects of the nuclear receptor RXRα.Cellular & molecular biology letters · 2018Review
- Modulation of nongenomic activation of PI3K signalling by tetramerization of N-terminally-cleaved RXRα.Nature communications · 2017Article
- Antagonist-perturbation mechanism for activation function-2 fixed motifs: active conformation and docking mode of retinoid X receptor antagonists.Journal of computer-aided molecular design · 2017Article
- Origin of an ancient hormone/receptor couple revealed by resurrection of an ancestral estrogen.Science advances · 2017Article
- Structure of the homodimeric androgen receptor ligand-binding domain.Nature communications · 2017Article
- Identification of a New RXRα Antagonist Targeting the Coregulator-Binding Site.ACS medicinal chemistry letters · 2014Article
- Dual RXR Agonists and RAR Antagonists Based on the Stilbene Retinoid Scaffold.ACS medicinal chemistry letters · 2014Article
- Vestigialization of an allosteric switch: genetic and structural mechanisms for the evolution of constitutive activity in a steroid hormone receptor.PLoS genetics · 2014Article
- Agonist and antagonist binding to the nuclear vitamin D receptor: dynamics, mutation effects and functional implications.In silico pharmacology · 2013Article
- General molecular biology and architecture of nuclear receptors.Current topics in medicinal chemistry · 2012Review
- Alcohol and aldehyde dehydrogenases: retinoid metabolic effects in mouse knockout models.Biochimica et biophysica acta · 2012Review
- Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.Molecular endocrinology (Baltimore, Md.) · 2010Article
- A comprehensive analysis of sequence variants and putative disease-causing mutations in photoreceptor-specific nuclear receptor NR2E3.Molecular vision · 2009Article
- Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- The NR4A nuclear receptor family in eosinophils.Journal of human genetics · 2007Review
- Neofunctionalization in vertebrates: the example of retinoic acid receptors.PLoS genetics · 2006Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of a single residue in the retinoid X receptor alpha (RXRalpha) ligand-binding pocket (LBP) generate constitutive, ligand-binding-competent mutants with structural and functional characteristics similar to those of agonist-bound wild-type RXR. Modelling of the mouse RXRalphaF318A LBP suggests that, like agonist binding, the mutation disrupts a cluster of van der Waals interactions that maintains helix H11 in the apo-receptor location, thereby shifting the thermodynamic equilibrium to the holo form. Heterodimerization with some apo-receptors (retinoic acid, thyroid hormone and vitamin D3 receptors) results in 'silencing' of RXRalphaF318A constitutive activity, which, on the other hand, efficiently contributes to synergistic transactivation within NGFI-B-RXR heterodimers. RAR mutants disabled for corepressor binding and/or lacking a functional AF-2 activation domain, do not relieve RXR 'silencing'. Not only RAR agonists, but also the RAR antagonist BMS614 induce conformational changes allowing RXR to exert constitutive (RXRalphaF318A) or agonist-induced (wild-type RXR) activity in heterodimers. Interestingly, the RXRalphaF318A constitutive activity generated within heterodimers in the presence of BMS614 requires the integrity of both RXR and RAR AF-2 domains. These observations suggest that, within RXR-RAR heterodimers, RAR can adopt a structure distinct from that of the active holo-RAR, thus allowing RXR to become transcriptionally responsive to agonists.
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