ArticleeLife2018
Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
26 citing papers in PubMed.
- Review
- Activation dynamics of a water-soluble human mu-opioid receptor.The Journal of biological chemistry · 2026Article
- A mu-opioid receptor positive allosteric modulator provides opioid-sparing antinociception without enhancing opioid side effects.The Journal of pharmacology and experimental therapeutics · 2026Article
- Investigating Endogenous Opioids Unravels the Mechanisms Behind Opioid-Induced Constipation, a Mathematical Modeling Approach.International journal of molecular sciences · 2025Article
- Article
- Article
- Structures of drug-specific monoclonal antibodies bound to opioids and nicotine reveal a common mode of binding.Structure (London, England : 1993) · 2023Article
- Investigating G-protein coupled receptor signalling with light-emitting biosensors.Frontiers in physiology · 2023Review
- Modular Peroxidase-Based Reporters for Detecting Protease Activity and Protein Interactions with Temporal Gating.Journal of the American Chemical Society · 2022Article
- Finding the Perfect Fit: Conformational Biosensors to Determine the Efficacy of GPCR Ligands.ACS pharmacology & translational science · 2022Review
- A Modular Fluorescent Sensor Motif Used to Detect Opioids, Protein-Protein Interactions, and Protease Activity.ACS chemical biology · 2022Article
- Intracellular VHHs to monitor and modulate GPCR signaling.Frontiers in endocrinology · 2022Review
- Accelerating GPCR Drug Discovery With Conformation-Stabilizing VHHs.Frontiers in molecular biosciences · 2022Review
- Article
- Reply to Zhuang et al.: Potential side effects of positive allosteric modulators of the mu-opioid receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- DEER Analysis of GPCR Conformational Heterogeneity.Biomolecules · 2021Review
- Article
- Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Allosteric communication regulates ligand-specific GPCR activity.The FEBS journal · 2021Review
- Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators.Frontiers in chemistry · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
The intrinsic efficacy of orthosteric ligands acting at G-protein-coupled receptors (GPCRs) reflects their ability to stabilize active receptor states (R*) and is a major determinant of their physiological effects. Here, we present a direct way to quantify the efficacy of ligands by measuring the binding of a R*-specific biosensor to purified receptor employing interferometry. As an example, we use the mu-opioid receptor (µ-OR), a prototypic class A GPCR, and its active state sensor, nanobody-39 (Nb39). We demonstrate that ligands vary in their ability to recruit Nb39 to µ-OR and describe methadone, loperamide, and PZM21 as ligands that support unique R* conformation(s) of µ-OR. We further show that positive allosteric modulators of µ-OR promote formation of R* in addition to enhancing promotion by orthosteric agonists. Finally, we demonstrate that the technique can be utilized with heterotrimeric G protein. The method is cell-free, signal transduction-independent and is generally applicable to GPCRs.
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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.