ArticleProceedings of the National Academy of Sciences of the United States of America2009
The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 243 citations in OpenAlex.
- Pooled it
- Unveiling the impact of colonic pH and pH-sensing receptors in blood pressure regulation.Gut microbes · 2026Review
- Innovative Approach Reveals How Receptors Control G Protein State Equilibria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Energy Landscape Sampling Reveals Ligand-Dependent Structural Dynamics of the Protease-Activated Receptor 1.Journal of chemical information and modeling · 2026Article
- Nano-GAngewandte Chemie (International ed. in English) · 2026Article
- Emergent eukaryotic directional sensing via receptor degradation and diffusion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Characterization of the GTPγS release function of a G protein-coupled receptor.Nature communications · 2025Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Single-Molecule Insights into GPCR Conformational Landscapes.The Journal of membrane biology · 2025Review
- Molecular insights into the modulation of the 5HTFEBS letters · 2025Article
- GPCRVS - AI-driven Decision Support System for GPCR Virtual Screening.International journal of molecular sciences · 2025Article
- Exploring the constitutive activation mechanism of the class A orphan GPR20.Acta pharmacologica Sinica · 2025Article
- Positive allosteric modulation of a GPCR ternary complex.Science advances · 2024Article
- Structural basis of Frizzled 4 in recognition of Dishevelled 2 unveils mechanism of WNT signaling activation.Nature communications · 2024Article
- Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq.Communications biology · 2024Article
- Probing Activation and Conformational Dynamics of the Vesicle-Reconstituted βThe journal of physical chemistry. B · 2024Article
- The chemokine receptor CCR5: multi-faceted hook for HIV-1.Retrovirology · 2024Review
- The complex nature of CXCR4 mutations in WHIM syndrome.Frontiers in immunology · 2024Review
- Single-molecule visualization of human ACommunications biology · 2023Article
- Upregulation of fibronectin and its integrin receptors - an adaptation to isolation stress that facilitates tumor initiation.Journal of cell science · 2023Article
86 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
8 authors at 3 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptors (GPCRs) mediate the majority of physiologic responses to hormones and neurotransmitters. However, many GPCRs exhibit varying degrees of agonist-independent G protein activation. This phenomenon is referred to as basal or constitutive activity. For many of these GPCRs, drugs classified as inverse agonists can suppress basal activity. There is a growing body of evidence that basal activity is physiologically relevant, and the ability of a drug to inhibit basal activity may influence its therapeutic properties. However, the molecular mechanism for basal activation and inhibition of basal activity by inverse agonists is poorly understood and difficult to study, because the basally active state is short-lived and represents a minor fraction of receptor conformations. Here, we investigate basal activation of the G protein Gs by the beta(2) adrenergic receptor (beta(2)AR) by using purified receptor reconstituted into recombinant HDL particles with a stoichiometric excess of Gs. The beta(2)AR is site-specifically labeled with a small, environmentally sensitive fluorophore enabling direct monitoring of agonist- and Gs-induced conformational changes. In the absence of an agonist, the beta(2)AR and Gs can be trapped in a complex by enzymatic depletion of guanine nucleotides. Formation of the complex is enhanced by the agonist isoproterenol, and it rapidly dissociates on exposure to concentrations of GTP and GDP found in the cytoplasm. The inverse agonist ICI prevents formation of the beta(2)AR-Gs complex, but has little effect on preformed complexes. These results provide insights into G protein-induced conformational changes in the beta(2)AR and the structural basis for ligand efficacy.
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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.