ArticleThe Journal of biological chemistry2017
Structural studies unravel the active conformation of apo RORγt nuclear receptor and a common inverse agonism of two diverse classes of RORγt inhibitors.
Article in The Journal of biological chemistry, 2017. 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, 59 citations in OpenAlex.
- The retinoic acid-related orphan receptors (RORs) signaling axis in skeletal homeostasis: mechanistic insights and chronotherapeutic prospects.Annals of medicine · 2026Review
- Large-scale comparative virtual screening identifies novel molecular targets underlying the multi-target activity of quercetin in psoriasis.Inflammopharmacology · 2026Article
- Snapshots of Motion: A Novel Structural Intermediate Reveals Conserved Dynamics in Archaeal DNA Ligases.Proteins · 2026Article
- Primulagenin A is a potent inverse agonist of the nuclear receptor RAR-related orphan receptor gamma (RORActa pharmaceutica Sinica. B · 2026Article
- Identification of New Lupane-Type Triterpenoids as Inverse Agonists of RAR-Related Orphan Receptor Gamma (RORγ).Journal of natural products · 2025Article
- Identification of a Novel Indolizine RORγT Inverse Agonist Using the AI-Driven Drug Design Platform.ACS medicinal chemistry letters · 2025Article
- Novel RORγt inverse agonists limit IL-17-mediated liver inflammation and fibrosis.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Article
- B-factor prediction in proteins using a sequence-based deep learning model.Patterns (New York, N.Y.) · 2023Article
- Discovery, Synthesis, and In Vitro Characterization of 2,3 Derivatives of 4,5,6,7-Tetrahydro-Benzothiophene as Potent Modulators of Retinoic Acid Receptor-Related Orphan Receptor γt.Journal of medicinal chemistry · 2023Article
- Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases.Journal of pharmaceutical analysis · 2023Review
- Virtual Screening Strategy to Identify Retinoic Acid-Related Orphan Receptor γt Modulators.Molecules (Basel, Switzerland) · 2023Article
- Recent applications of computational methods to allosteric drug discovery.Frontiers in molecular biosciences · 2022Review
- Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ.Frontiers in molecular biosciences · 2022Article
- Structure-Activity Relationship Studies of Trisubstituted Isoxazoles as Selective Allosteric Ligands for the Retinoic-Acid-Receptor-Related Orphan Receptor γt.Journal of medicinal chemistry · 2021Article
- Structure of an inactive conformation of GTP-bound RhoA GTPase.Structure (London, England : 1993) · 2021Article
- Covalent Occlusion of the RORγt Ligand Binding Pocket Allows Unambiguous Targeting of an Allosteric Site.ACS medicinal chemistry letters · 2021Article
- Orthosteric and Allosteric Dual Targeting of the Nuclear Receptor RORγt with a Bitopic Ligand.ACS chemical biology · 2021Article
- BANΔIT: B'-Factor Analysis for Drug Design and Structural Biology.Molecular informatics · 2021Article
- Transcriptomic effects of rs4845604, an IBD and allergy-associated RORC variant, in stimulated ex vivo CD4+ T cells.PloS one · 2021Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear receptor retinoid acid receptor-related orphan receptor γt (RORγt) is a master regulator of the Th17/IL-17 pathway that plays crucial roles in the pathogenesis of autoimmunity. RORγt has recently emerged as a highly promising target for treatment of a number of autoimmune diseases. Through high-throughput screening, we previously identified several classes of inverse agonists for RORγt. Here, we report the crystal structures for the ligand-binding domain of RORγt in both apo and ligand-bound states. We show that apo RORγt adopts an active conformation capable of recruiting coactivator peptides and present a detailed analysis of the structural determinants that stabilize helix 12 (H12) of RORγt in the active state in the absence of a ligand. The structures of ligand-bound RORγt reveal that binding of the inverse agonists disrupts critical interactions that stabilize H12. This destabilizing effect is supported by
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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.