ArticleProceedings of the National Academy of Sciences of the United States of America2016
Decay of an active GPCR: Conformational dynamics govern agonist rebinding and persistence of an active, yet empty, receptor state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Trial
- Biophysical and structural analysis of human green cone opsin.Biophysical journal · 2026Article
- A key amino acid site associated with rhodopsin mammal evolution to diurnal vision.Scientific reports · 2025Article
- Article
- A rapid, tag-free way to purify functional GPCRs.The Journal of biological chemistry · 2024Article
- A short story on how chromophore is hydrolyzed from rhodopsin for recycling.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Physiology, Pharmacology, and Genetics.Molecules (Basel, Switzerland) · 2023Review
- Adaptation of Antarctic Icefish Vision to Extreme Environments.Molecular biology and evolution · 2023Article
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Relevance to μ Opioid Receptors in Analgesia and Addiction.Molecules (Basel, Switzerland) · 2022Review
- FRET sensors reveal the retinal entry pathway in the G protein-coupled receptor rhodopsin.iScience · 2022Article
- Kinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling.Nature communications · 2022Article
- Novel fluorescent GPCR biosensor detects retinal equilibrium binding to opsin and active G protein and arrestin signaling conformations.The Journal of biological chemistry · 2020Article
- Structural insights into differences in G protein activation by family A and family B GPCRs.Science (New York, N.Y.) · 2020Article
- Minute-scale persistence of a GPCR conformation state triggered by non-cognate G protein interactions primes signaling.Nature communications · 2019Article
- Conformational Transitions and the Activation of Heterotrimeric G Proteins by G Protein-Coupled Receptors.ACS pharmacology & translational science · 2019Article
- Differentiating between Inactive and Active States of Rhodopsin by Atomic Force Microscopy in Native Membranes.Analytical chemistry · 2019Article
- Apo-Opsin Exists in Equilibrium Between a Predominant Inactive and a Rare Highly Active State.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Structural insights into binding specificity, efficacy and bias of a βNature chemical biology · 2018Article
- Article
- Ligand channel in pharmacologically stabilized rhodopsin.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Here, we describe two insights into the role of receptor conformational dynamics during agonist release (all-trans retinal, ATR) from the visual G protein-coupled receptor (GPCR) rhodopsin. First, we show that, after light activation, ATR can continually release and rebind to any receptor remaining in an active-like conformation. As with other GPCRs, we observe that this equilibrium can be shifted by either promoting the active-like population or increasing the agonist concentration. Second, we find that during decay of the signaling state an active-like, yet empty, receptor conformation can transiently persist after retinal release, before the receptor ultimately collapses into an inactive conformation. The latter conclusion is based on time-resolved, site-directed fluorescence labeling experiments that show a small, but reproducible, lag between the retinal leaving the protein and return of transmembrane helix 6 (TM6) to the inactive conformation, as determined from tryptophan-induced quenching studies. Accelerating Schiff base hydrolysis and subsequent ATR dissociation, either by addition of hydroxylamine or introduction of mutations, further increased the time lag between ATR release and TM6 movement. These observations show that rhodopsin can bind its agonist in equilibrium like a traditional GPCR, provide evidence that an active GPCR conformation can persist even after agonist release, and raise the possibility of targeting this key photoreceptor protein by traditional pharmaceutical-based treatments.
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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.