ArticleAngewandte Chemie (International ed. in English)2015
Identification of a Conformational Equilibrium That Determines the Efficacy and Functional Selectivity of the μ-Opioid Receptor.
Article in Angewandte Chemie (International ed. in English), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 132 citations in OpenAlex.
- Extended local deuteration of leucine enhances methyl NMR of large proteins expressed in eukaryotic cells.Chemical communications (Cambridge, England) · 2026Article
- Rational design of a Kappa opioid receptor peptide agonist with attenuated β-arrestin signaling.Nature communications · 2026Article
- The Role of Intrinsically Disordered Domains in Regulating G Protein-Coupled Receptor Signaling.Journal of the American Chemical Society · 2026Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- The role of intrinsically disordered domains in regulating G protein coupled receptor signaling.bioRxiv : the preprint server for biology · 2025Article
- Structure and dynamics determine G protein coupling specificity at a class A GPCR.Science advances · 2025Article
- Biased activation of the vasopressin V2 receptor probed by molecular dynamics simulations, NMR and pharmacological studies.Computational and structural biotechnology journal · 2024Article
- G Protein-Coupled Receptors: A Century of Research and Discovery.Circulation research · 2024Review
- Structural and dynamic insights into the activation of the μ-opioid receptor by an allosteric modulator.Nature communications · 2024Article
- Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1.Nature communications · 2023Article
- Illuminating GPCR signaling mechanisms by NMR spectroscopy with stable-isotope labeled receptors.Current opinion in pharmacology · 2023Review
- Dynamics of the Apo µ-Opioid Receptor in Complex with Gi Protein.International journal of molecular sciences · 2023Article
- Bringing GPCR Structural Biology to Medical Applications: Insights from Both V2 Vasopressin and Mu-Opioid Receptors.Membranes · 2023Review
- Ligands selectively tune the local and global motions of neurotensin receptor 1 (NTSCell reports · 2023Article
- Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor.Nature communications · 2023Article
- Evaluation of the Intracellular Signaling Activities of κ-Opioid Receptor Agonists, Nalfurafine Analogs; Focusing on the Selectivity of G-Protein- and β-Arrestin-Mediated Pathways.Molecules (Basel, Switzerland) · 2022Article
- G Protein-coupled Receptor (GPCR) Reconstitution and Labeling for Solution Nuclear Magnetic Resonance (NMR) Studies of the Structural Basis of Transmembrane Signaling.Molecules (Basel, Switzerland) · 2022Review
- Activation mechanism of the μ-opioid receptor by an allosteric modulator.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural basis of sphingosine-1-phosphate receptor 1 activation and biased agonism.Nature chemical biology · 2022Article
- Metadynamics simulations leveraged by statistical analyses and artificial intelligence-based tools to inform the discovery of G protein-coupled receptor ligands.Frontiers in endocrinology · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G-protein-coupled receptor (GPCR) ligands impart differing degrees of signaling in the G-protein and arrestin pathways, in phenomena called "biased signaling". However, the mechanism underlying the biased signaling of GPCRs is still unclear, although crystal structures of GPCRs bound to the G protein or arrestin are available. In this study, we observed the NMR signals from methionine residues of the μ-opioid receptor (μOR) in the balanced- and biased-ligand-bound states. We found that the intracellular cavity of μOR exists in an equilibrium between closed and multiple open conformations with coupled conformational changes on the transmembrane helices 3, 5, 6, and 7, and that the population of each open conformation determines the G-protein- and arrestin-mediated signaling levels in each ligand-bound state. These findings provide insight into the biased signaling of GPCRs and will be helpful for development of analgesics that stimulate μOR with reduced tolerance and dependence.
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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.