ArticleThe Journal of biological chemistry2014
Defining the communication between agonist and coactivator binding in the retinoid X receptor α ligand binding domain.
Article in The Journal of biological chemistry, 2014. 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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Who cites it
20 citing papers in PubMed, 52 citations in OpenAlex.
- A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers.Cancer prevention research (Philadelphia, Pa.) · 2019Trial
- Ligand Screening System for the RXRα Heterodimer Using the Fluorescence RXR Agonist CU-6PMN.ACS medicinal chemistry letters · 2023Article
- Next-generation retinoid X receptor agonists increase ATRA signaling in organotypic epithelium cultures and have distinct effects on receptor dynamics.The Journal of biological chemistry · 2023Article
- Conformationally Defined Rexinoids for the Prevention of Inflammation and Nonmelanoma Skin Cancers.Journal of medicinal chemistry · 2022Article
- Stability of the Retinoid X Receptor-α Homodimer in the Presence and Absence of Rexinoid and Coactivator Peptide.Biochemistry · 2021Article
- Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.Journal of cellular and molecular medicine · 2021Article
- Identification of Small-Molecule Regulators of Testicular Receptor 4 via a Drug Repurposing Screening.ACS omega · 2020Article
- Comprehensive Set of Tertiary Complex Structures and Palmitic Acid Binding Provide Molecular Insights into Ligand Design for RXR Isoforms.International journal of molecular sciences · 2020Article
- A molecular switch regulating transcriptional repression and activation of PPARγ.Nature communications · 2020Article
- Computer-Assisted Discovery and Structural Optimization of a Novel Retinoid X Receptor Agonist Chemotype.ACS medicinal chemistry letters · 2019Article
- Neuroprotective effect of naturally occurring RXR agonists isolated from Sophora tonkinensis Gagnep. on amyloid-β-induced cytotoxicity in PC12 cells.Journal of natural medicines · 2019Article
- Article
- How α-Helical Motifs Form Functionally Diverse Lipid-Binding Compartments.Annual review of biochemistry · 2017Review
- Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.Current topics in medicinal chemistry · 2017Review
- Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.Molecular cancer therapeutics · 2016Article
- Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.PloS one · 2016Article
- Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancers.Journal of medicinal chemistry · 2015Article
- Applications of hydrogen/deuterium exchange MS from 2012 to 2014.Analytical chemistry · 2015Review
- Methyl substitution of a rexinoid agonist improves potency and reveals site of lipid toxicity.Journal of medicinal chemistry · 2014Article
- Methyl-substituted conformationally constrained rexinoid agonists for the retinoid X receptors demonstrate improved efficacy for cancer therapy and prevention.Bioorganic & medicinal chemistry · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Retinoid X receptors (RXRs) are obligate partners for several other nuclear receptors, and they play a key role in several signaling processes. Despite being a promiscuous heterodimer partner, this nuclear receptor is a target of therapeutic intervention through activation using selective RXR agonists (rexinoids). Agonist binding to RXR initiates a large conformational change in the receptor that allows for coactivator recruitment to its surface and enhanced transcription. Here we reveal the structural and dynamical changes produced when a coactivator peptide binds to the human RXRα ligand binding domain containing two clinically relevant rexinoids, Targretin and 9-cis-UAB30. Our results show that the structural changes are very similar for each rexinoid and similar to those for the pan-agonist 9-cis-retinoic acid. The four structural changes involve key residues on helix 3, helix 4, and helix 11 that move from a solvent-exposed environment to one that interacts extensively with helix 12. Hydrogen-deuterium exchange mass spectrometry reveals that the dynamics of helices 3, 11, and 12 are significantly decreased when the two rexinoids are bound to the receptor. When the pan-agonist 9-cis-retinoic acid is bound to the receptor, only the dynamics of helices 3 and 11 are reduced. The four structural changes are conserved in all x-ray structures of the RXR ligand-binding domain in the presence of agonist and coactivator peptide. They serve as hallmarks for how RXR changes conformation and dynamics in the presence of agonist and coactivator to initiate signaling.
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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.