ArticleThe Journal of biological chemistry2013
Detection of G protein-selective G protein-coupled receptor (GPCR) conformations in live cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Pooled it
- Molecular Determinants of G Protein Subtype-Specific Coupling to the Angiotensin II Type 1 Receptor.bioRxiv : the preprint server for biology · 2026Article
- Selective positive allosteric modulation of βNature communications · 2026Article
- A luminescent calcium biosensor enabling endpoint measurement of GPCR-mediated calcium signaling.Communications biology · 2026Article
- Light-Based Molecular Tools to Precisely Monitor and Operate β-Adrenoceptors.Medicinal research reviews · 2026Review
- Future Directions in GPCR Biased Signaling and Ligand Pharmacology.Handbook of experimental pharmacology · 2026Review
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals.Chemical reviews · 2024Review
- Class-Wide Analysis of Frizzled-Dishevelled Interactions Using BRET Biosensors Reveals Functional Differences among Receptor Paralogs.ACS sensors · 2024Article
- Bayesian network models identify cooperative GPCR:G protein interactions that contribute to G protein coupling.The Journal of biological chemistry · 2024Article
- Rules and mechanisms governing G protein coupling selectivity of GPCRs.Cell reports · 2023Article
- Bayesian network models identify co-operative GPCR:G protein interactions that contribute to G protein coupling.bioRxiv : the preprint server for biology · 2023Article
- Advancements in G protein-coupled receptor biosensors to study GPCR-G protein coupling.British journal of pharmacology · 2023Review
- Article
- Investigating G-protein coupled receptor signalling with light-emitting biosensors.Frontiers in physiology · 2023Review
- In silico identification of a βProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Dynamic spatiotemporal determinants modulate GPCR:G protein coupling selectivity and promiscuity.Nature communications · 2022Article
- Examination of Intracellular GPCR-Mediated Signaling with High Temporal Resolution.International journal of molecular sciences · 2022Article
- Kinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling.Nature communications · 2022Article
- Genetically encoded fluorescent biosensors for GPCR research.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although several recent studies have reported that GPCRs adopt multiple conformations, it remains unclear how subtle conformational changes are translated into divergent downstream responses. In this study, we report on a novel class of FRET-based sensors that can detect the ligand/mutagenic stabilization of GPCR conformations that promote interactions with G proteins in live cells. These sensors rely on the well characterized interaction between a GPCR and the C terminus of a Gα subunit. We use these sensors to elucidate the influence of the highly conserved (E/D)RY motif on GPCR conformation. Specifically, Glu/Asp but not Arg mutants of the (E/D)RY motif are known to enhance basal GPCR signaling. Hence, it is unclear whether ionic interactions formed by the (E/D)RY motif (ionic lock) are necessary to stabilize basal GPCR states. We find that mutagenesis of the β2-AR (E/D)RY ionic lock enhances interaction with Gs. However, only Glu/Asp but not Arg mutants increase G protein activation. In contrast, mutagenesis of the opsin (E/D)RY ionic lock does not alter its interaction with transducin. Instead, opsin-specific ionic interactions centered on residue Lys-296 are both necessary and sufficient to promote interactions with transducin. Effective suppression of β2-AR basal activity by inverse agonist ICI 118,551 requires ionic interactions formed by the (E/D)RY motif. In contrast, the inverse agonist metoprolol suppresses interactions with Gs and promotes Gi binding, with concomitant pertussis toxin-sensitive inhibition of adenylyl cyclase activity. Taken together, these studies validate the use of the new FRET sensors while revealing distinct structural mechanisms for ligand-dependent GPCR function.
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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.