ArticleNature2015
Propagation of conformational changes during μ-opioid receptor activation.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 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.
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
149 citing papers in PubMed, 256 citations in OpenAlex.
- From empirical screening to lipid trolling: the evolution of extrahelical allosteric modulators of AMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- G Protein-Mediated Allosteric Modulation of Ligand Binding in Class A GPCRs: Receptor-Ligand-Transducer Ensembles in Disease and Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Elucidating the Structure and Activation Mechanisms of GPCRs Using Modern Computational and AI Tools.Cell biochemistry and biophysics · 2026Review
- Activation dynamics of a water-soluble human mu-opioid receptor.The Journal of biological chemistry · 2026Article
- Discovery and dynamic pharmacology of μ-opioid receptor positive allosteric modulators.bioRxiv : the preprint server for biology · 2026Article
- Structure-Bias Relationship of μ-Opioid Receptor Agonists.Handbook of experimental pharmacology · 2026Review
- Antibody-enabled structural biology and AI-driven antibody design.Frontiers in pharmacology · 2026Review
- Article
- N-(3-Hydroxyphenyl)-3,8-diazabicyclooctanes as opioid receptors probes. 1. Investigation of the phenolic hydroxyl group.European journal of medicinal chemistry · 2025Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor.Journal of chemical information and modeling · 2025Article
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- CXC Chemokine Ligand 12 Facilitates Gi Protein Binding to CXC Chemokine Receptor 4 by Stabilizing Packing of the Proline-Isoleucine-Phenylalanine Motif: Insights from Automated Path Searching.Journal of the American Chemical Society · 2025Article
- Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.Journal of chemical information and modeling · 2025Article
- Exploring the constitutive activation mechanism of the class A orphan GPR20.Acta pharmacologica Sinica · 2025Article
- Impact of Intracellular Proteins on μ-Opioid Receptor Structure and Ligand Binding.The journal of physical chemistry. B · 2025Article
- Effects of pH on opioid receptor activation and implications for drug design.Biophysical journal · 2024Review
- Intracellular pocket conformations determine signaling efficacy through thebioRxiv : the preprint server for biology · 2024Article
- Biased activation of the vasopressin V2 receptor probed by molecular dynamics simulations, NMR and pharmacological studies.Computational and structural biotechnology journal · 2024Article
- Agonist activation to open the Gα subunit of the GPCR-G protein precoupled complex defines functional agonist activation of TAS2R5.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
µ-Opioid receptors (µORs) are G-protein-coupled receptors that are activated by a structurally diverse spectrum of natural and synthetic agonists including endogenous endorphin peptides, morphine and methadone. The recent structures of the μOR in inactive and agonist-induced active states (Huang et al., ref. 2) provide snapshots of the receptor at the beginning and end of a signalling event, but little is known about the dynamic sequence of events that span these two states. Here we use solution-state NMR to examine the process of μOR activation using a purified receptor (mouse sequence) preparation in an amphiphile membrane-like environment. We obtain spectra of the μOR in the absence of ligand, and in the presence of the high-affinity agonist BU72 alone, or with BU72 and a G protein mimetic nanobody. Our results show that conformational changes in transmembrane segments 5 and 6 (TM5 and TM6), which are required for the full engagement of a G protein, are almost completely dependent on the presence of both the agonist and the G protein mimetic nanobody, revealing a weak allosteric coupling between the agonist-binding pocket and the G-protein-coupling interface (TM5 and TM6), similar to that observed for the β2-adrenergic receptor. Unexpectedly, in the presence of agonist alone, we find larger spectral changes involving intracellular loop 1 and helix 8 compared to changes in TM5 and TM6. These results suggest that one or both of these domains may play a role in the initial interaction with the G protein, and that TM5 and TM6 are only engaged later in the process of complex formation. The initial interactions between the G protein and intracellular loop 1 and/or helix 8 may be involved in G-protein coupling specificity, as has been suggested for other family A G-protein-coupled receptors.
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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.