ArticleNature communications2025
Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Compensatory pathways in tryptophan metabolism and immune regulation following IDO inhibition.Molecular biology reports · 2026Review
- Perfluorooctane sulfonate (PFOS) interferes with Cyp1a activity and dysregulates the aryl hydrocarbon receptor pathway in larval zebrafish (Danio rerio).Environmental pollution (Barking, Essex : 1987) · 2026Article
- Cooperation or Conflict? Molecular and Physiological Cross-Talk Between the Aryl Hydrocarbon and Vitamin D Receptors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Juvenile hormone receptor relies on conserved domain interfaces for dimerization-dependent activity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell-Specific Modulation of the Aryl Hydrocarbon Receptor by Kynurenine in Pulmonary Fibrosis Requires Microenvironmental Crosstalk.bioRxiv : the preprint server for biology · 2026Article
- Microbiota-Derived Metabolites in the Epigenetic Regulation of Redox Homeostasis.Antioxidants (Basel, Switzerland) · 2026Review
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- Distinct 2-phenylimidazo[1,2-iScience · 2026Article
- Hypoxia-inducible factors: Regulatory functions and status as a therapeutic target in gastric cancer (Review).Oncology letters · 2026Review
- Combination of Chromatographic and Machine Learning-Driven Virtual Fractionation Identifies Aryl Hydrocarbon Receptor Agonists in Sediments.Environmental science & technology · 2026Article
- AHR: The Overlooked Mediator in SkincareBridging Environmental Sensing and Skin Physiology.Environment & health (Washington, D.C.) · 2026Review
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Evaluating the Effects of Neburon Exposure on Ovarian Folliculogenesis Using Zebrafish and Mouse Granulosa Cell Line.Environmental health perspectives · 2026Article
- Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- AHR/NRF2 Dual Agonist Prediction and Natural Compound Screening Based on Machine Learning: A New Strategy for the Treatment of Atopic Dermatitis.International journal of molecular sciences · 2026Article
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- Exploration of Agonist and Antagonist Binding Sites within the Cytosolic AHR Complex Using Molecular Modeling.ACS omega · 2026Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- The Role of Aryl Hydrocarbon Receptor in Airway Remodeling: Mechanistic Insights Across Cellular Functions.Clinical reviews in allergy & immunology · 2026Review
- Intestinal epithelial AhR deletion aggravates DSS-induced colitis via lipid- and amino-acid metabolic reprogramming: integrated metabolomic-transcriptomic evidence.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The aryl hydrocarbon receptor (AHR) possesses an extraordinary capacity to sense and respond to a wide range of small-molecule ligands, ranging from polycyclic aromatic hydrocarbons to endogenous compounds. Upon ligand binding, AHR translocates from the cytoplasm to nucleus, forming a transcriptionally active complex with aryl hydrocarbon receptor nuclear translocator (ARNT), for DNA binding and initiation of gene expression programs that include cellular detoxification pathways and immune responses. Here, we examine the molecular mechanisms governing AHR's high-affinity binding and activation by a diverse group of ligands. Crystal structures of the AHR-ARNT-DNA complexes, bound with each of six established AHR ligands, including Tapinarof, 6-formylindolo[3,2-b]carbazole (FICZ), benzo[a]pyrene (BaP), β-naphthoflavone (BNF), Indigo and Indirubin, reveal an unconventional mode of subunit assembly with intimate association between the PAS-B domains of AHR and ARNT. AHR's PAS-B domain utilizes eight conserved residues whose dynamic rearrangements account for the ability to bind to ligands through hydrophobic and π-π interactions. Our findings further reveal the structural underpinnings of a ligand-driven activation mechanism, whereby a segment of the AHR protein undergoes a structural transition from chaperone engagement to ARNT heterodimer stabilization, to generate the transcriptionally competent assembly. Our results provide key information for the future development of AHR-targeting drugs.
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