ArticleNucleic acids research2022
The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 28 citations in OpenAlex.
- Beyond the canonical view: steroid receptor network plasticity and mechanosensitive chromatin integration in breast cancer.NAR cancer · 2026Review
- Corticosteroids in asthma and COPD: an inflammopharmacological perspective on molecular and genetic determinants.Molecular biology reports · 2026Review
- A Molecular-Dynamics-Guided Screening Pipeline Identifies Topical Glucocorticoid Receptor Modulators with Selective Epidermal Activation.Skin pharmacology and physiology · 2026Article
- Endocrine regulation of the hepatic fasting response: cues, cooperation and consequences.Nature reviews. Endocrinology · 2026Review
- Clocks on steroids: how glucocorticoid receptors tell cells the time.The Journal of endocrinology · 2026Review
- Mineralocorticoid and glucocorticoid receptor heterodimers mediate cortisol-induced behavioural changes via modulation of glutamatergic signalling.Molecular psychiatry · 2026Article
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- Modeling Protein-Protein Complexes by Combining pyDock and AlphaFold.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The multimerization pathway of the glucocorticoid receptor.Nucleic acids research · 2025Article
- Celebrating 50 years of fluorescence correlation spectroscopy (FCS): Advancing live-cell massively parallel FCS studies with photostable GFPs, mStayGold and StayGold/E138D.Biochimica et biophysica acta. General subjects · 2025Article
- Mineralocorticoid receptor phase separation modulates cardiac preservation.Nature cardiovascular research · 2025Article
- Bile acids target an exposed cavity in the glucocorticoid receptor modulating receptor self-assembly, chromatin binding and transcriptional activity.bioRxiv : the preprint server for biology · 2025Article
- Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers.Nucleic acids research · 2025Article
- Glucocorticoid receptor controls atopic dermatitis inflammation via functional interactions with P63 and autocrine signaling in epidermal keratinocytes.Cell death & disease · 2024Article
- The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.Endocrine reviews · 2024Review
- The mineralocorticoid receptor forms higher order oligomers upon DNA binding.Protein science : a publication of the Protein Society · 2024Article
- Review
- A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance.Science advances · 2023Article
- Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor.Frontiers in endocrinology · 2023Review
- Stereoisomers of an Aryl Pyrazole Glucocorticoid Receptor Agonist Scaffold Elicit Differing Anti-inflammatory Responses.ACS medicinal chemistry letters · 2022Article
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, the functional oligomeric state of the full-length receptor, which is essential for its transcriptional activity, remains disputed. Here we present five new crystal structures of agonist-bound GR-LBD, along with a thorough analysis of previous structural work. We identify four distinct homodimerization interfaces on the GR-LBD surface, which can associate into 20 topologically different homodimers. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution, quantitative fluorescence microscopy in living cells, and transcriptomic analyses. Our results highlight the relevance of non-canonical dimerization modes for GR, especially of contacts made by loop L1-3 residues such as Tyr545. Our work illustrates the unique flexibility of GR's LBD and suggests different dimeric conformations within cells. In addition, we unveil pathophysiologically relevant quaternary assemblies of the receptor with important implications for glucocorticoid action and drug design.
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