ArticleMolecular cell2021
Molecular insights into the biased signaling mechanism of the μ-opioid receptor.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 76 citations in OpenAlex.
- Emerging Insights into the Distinct Pharmacological Mechanisms of Buprenorphine.Journal of chemical information and modeling · 2026Article
- A neurotensin receptor type 1-derived pepducin acts as a biased allosteric modulator to regulate target receptor function.Acta pharmaceutica Sinica. B · 2026Article
- Binding pose depth modulates photoswitchable ligands' efficacy at the 5-HTCommunications chemistry · 2026Article
- Structure-Bias Relationship of μ-Opioid Receptor Agonists.Handbook of experimental pharmacology · 2026Review
- Population prevalence of high-risk pharmacogenetic configurations in a healthy older Australian reference cohort.Frontiers in pharmacology · 2026Article
- Allosteric activation of a cell-type-specific GPR120 inhibits amyloid pathology of Alzheimer's disease.Nature aging · 2026Article
- The molecular basis of μ-opioid receptor signaling plasticity.Cell research · 2025Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Single-molecule characterization of opioid receptor heterodimers reveals soluble µ-δ dimer blocker peptide alleviates morphine tolerance.Nature communications · 2025Article
- Biased signalingActa pharmaceutica Sinica. B · 2025Review
- Multiple intramolecular triggers converge to preferential G protein coupling in the CBNature communications · 2025Article
- ProGuide: a flexible framework for modeling global conformational rearrangements in proteins using DEER-derived distance restraints.bioRxiv : the preprint server for biology · 2025Article
- Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor.Journal of chemical information and modeling · 2025Article
- Visualizing agonist-induced M2 receptor activation regulated by aromatic ring dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- How Ligands Achieve Biased Signaling toward Arrestins.Biochemistry · 2025Review
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.Journal of chemical information and modeling · 2025Article
- 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
- Biased Signaling Agonists Promote Distinct Phosphorylation and Conformational States of the Dopamine D3 Receptor.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
GPCR functional selectivity opens new opportunities for the design of safer drugs. Ligands orchestrate GPCR signaling cascades by modulating the receptor conformational landscape. Our study provides insights into the dynamic mechanism enabling opioid ligands to preferentially activate the G protein over the β-arrestin pathways through the μ-opioid receptor (μOR). We combine functional assays in living cells, solution NMR spectroscopy, and enhanced-sampling molecular dynamic simulations to identify the specific μOR conformations induced by G protein-biased agonists. In particular, we describe the dynamic and allosteric communications between the ligand-binding pocket and the receptor intracellular domains, through conserved motifs in class A GPCRs. Most strikingly, the biased agonists trigger μOR conformational changes in the intracellular loop 1 and helix 8 domains, which may impair β-arrestin binding or signaling. The findings may apply to other GPCR families and provide key molecular information that could facilitate the design of biased ligands.
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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.