ArticleNature communications2019
Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Molecular Dynamics of PPAR Nuclear Receptors: From Ligand Binding to Transcriptional Regulation.Cells · 2026Review
- An aerosolized dual-action autotaxin inhibitor-PPARγ agonist for the treatment of pulmonary fibrosis.Cell reports. Medicine · 2026Article
- Evaluation of 3',4'-Di-Biomolecules · 2026Article
- Predicting peroxisome proliferator-activated receptor gamma potency of small molecules: a synergistic consensus model and deep learning binding affinity approach powered by Enalos Cloud Platform.Molecular diversity · 2026Article
- Liquid Crystal Monomers and Their Mixtures Alter Nuclear Receptor Signaling and Promote Adipogenesis In Vitro.Endocrinology · 2025Article
- Review
- From Apo to Ligand-Bound: Unraveling PPARγ-LBD Conformational Shifts via Advanced Molecular Dynamics.ACS omega · 2025Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.Nature communications · 2025Article
- An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.Nature communications · 2025Article
- Agonists of the Nuclear Receptor PPARγ Can Produce Biased Signaling.Molecular pharmacology · 2024Article
- Oxidative Stress and the Nrf2/PPARγ Axis in the Endometrium: Insights into Female Fertility.Cells · 2024Review
- PPARγ Antagonists Exhibit Antitumor Effects by Regulating Ferroptosis and Disulfidptosis.Biomolecules · 2024Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.bioRxiv : the preprint server for biology · 2024Article
- Heat shock protein family A member 8 serving as a co-activator of transcriptional factor ETV4 up-regulates PHLDA2 to promote the growth of liver cancer.Acta pharmacologica Sinica · 2023Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy.Frontiers in pharmacology · 2023Review
- A structural mechanism of nuclear receptor biased agonism.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Community guidelines for GPCR ligand bias: IUPHAR review 32.British journal of pharmacology · 2022Review
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Discovery of Novel GR Ligands toward Druggable GR Antagonist Conformations Identified by MD Simulations and Markov State Model Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The repressive states of nuclear receptors (i.e., apo or bound to antagonists or inverse agonists) are poorly defined, despite the fact that nuclear receptors are a major drug target. Most ligand bound structures of nuclear receptors, including peroxisome proliferator-activated receptor γ (PPARγ), are similar to the apo structure. Here we use NMR, accelerated molecular dynamics and hydrogen-deuterium exchange mass spectrometry to define the PPARγ structural ensemble. We find that the helix 3 charge clamp positioning varies widely in apo and is stabilized by efficacious ligand binding. We also reveal a previously undescribed mechanism for inverse agonism involving an omega loop to helix switch which induces disruption of a tripartite salt-bridge network. We demonstrate that ligand binding can induce multiple structurally distinct repressive states. One state recruits peptides from two different corepressors, while another recruits just one, providing structural evidence of ligand bias in a nuclear receptor.
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Registered trials
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.