ArticleeLife2018
Cooperative cobinding of synthetic and natural ligands to the nuclear receptor PPARγ.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed.
- Dosing PPARγ Activation With Light Using Fast Relaxing Photoswitches.Angewandte Chemie (International ed. in English) · 2026Article
- The spatial architecture of tumor immunity: Emerging predictive biomarkers across cancer.Immunologic research · 2026Review
- Autoinhibition of untimely DNA binding by structural disorder in the full-length peroxisome proliferator-activated receptors (PPARs).Nature communications · 2026Article
- Molecular Dynamics of PPAR Nuclear Receptors: From Ligand Binding to Transcriptional Regulation.Cells · 2026Review
- RNF34 restrains endometriosis through SREBP1-dependent metabolic-immune crosstalk.Cellular and molecular life sciences : CMLS · 2026Article
- SGLT2 Inhibition as a Perioperative Cardiorenal Stabilizer in Cardiac Surgery: Integrated Clinical Cohort and Pleiotropic Network-Based Pharmacological Analysis.Journal of clinical medicine · 2026Article
- Article
- Potential neuroprotective and therapeutic agents and their mechanisms for irradiation-induced brain injury.Ibrain · 2026Review
- Supramolecular assembly of novel achatin structurally similar peptide as potential G protein-coupled receptors anticancer ligands: focus on its pseudo-macrocycle nature.Royal Society open science · 2025Article
- PPARG-centric transcriptional re-wiring during differentiation of human trophoblast stem cells into extravillous trophoblasts.Nucleic acids research · 2025Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.Nature communications · 2025Article
- Article
- Article
- Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ.bioRxiv : the preprint server for biology · 2024Article
- A new mode of inhibition.eLife · 2024Article
- Cladosporols and PPARγ: Same Gun, Same Bullet, More Targets.Biomolecules · 2024Review
- A Combined Molecular Dynamics and Hydropathic INTeraction (HINT) Approach to Investigate Protein Flexibility: The PPARγ Case Study.Molecules (Basel, Switzerland) · 2024Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.bioRxiv : the preprint server for biology · 2024Article
- PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges.Biomolecules · 2024Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Crystal structures of peroxisome proliferator-activated receptor gamma (PPARγ) have revealed overlapping binding modes for synthetic and natural/endogenous ligands, indicating competition for the orthosteric pocket. Here we show that cobinding of a synthetic ligand to the orthosteric pocket can push natural and endogenous PPARγ ligands (fatty acids) out of the orthosteric pocket towards an alternate ligand-binding site near the functionally important omega (Ω)-loop. X-ray crystallography, NMR spectroscopy, all-atom molecular dynamics simulations, and mutagenesis coupled to quantitative biochemical functional and cellular assays reveal that synthetic ligand and fatty acid cobinding can form a 'ligand link' to the Ω-loop and synergistically affect the structure and function of PPARγ. These findings contribute to a growing body of evidence indicating ligand binding to nuclear receptors can be more complex than the classical one-for-one orthosteric exchange of a natural or endogenous ligand with a synthetic ligand.
Indexed as
Identifiers
What OpenQuestion holds
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.