ArticleNature2010
Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 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
220 citing papers in PubMed, 1 synthesis or guideline pooled it, 468 citations in OpenAlex.
- Pooled it
- A Minimalist Model for Navigating Conformational Landscape Uncovers the Activation Mechanism of βACS physical chemistry Au · 2026Article
- Molecular mechanisms of native ligand selectivity in catecholamine G protein-coupled receptors.Nature communications · 2026Article
- Detection of an Antagonist Bound to the Neurokinin a Receptor in Styrene-Maleic Acid Lipid Particles byChembiochem : a European journal of chemical biology · 2026Article
- Elemental Selenium/Tellurium in Polymer Assemblies: Responsive Innovation.Polymer science & technology (Washington, D.C.) · 2026Review
- Biased Agonism at β-Adrenoceptor Subtypes: A Drug Development Perspective.Handbook of experimental pharmacology · 2026Review
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Development of an allosteric adhesion GPCR nanobody with therapeutic potential.Nature chemical biology · 2025Article
- Article
- Histamine-modulated wettability switching in G-protein-coupled receptor inspired nanochannel for potential drug screening and biosensing.Nature communications · 2025Article
- The clinical application progress of multimodal analgesia strategy in enhanced recovery after surgery: a narrative review.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Biased activation of the vasopressin V2 receptor probed by molecular dynamics simulations, NMR and pharmacological studies.Computational and structural biotechnology journal · 2024Article
- Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1.The journal of physical chemistry. B · 2024Article
- The sphingosine-1-phosphate receptor 1 mediates the atheroprotective effect of eicosapentaenoic acid.Nature metabolism · 2024Article
- Cellular lipids regulate the conformational ensembles of the disordered intracellular loop 3 in β2-adrenergic receptor.iScience · 2024Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Probing Activation and Conformational Dynamics of the Vesicle-Reconstituted βThe journal of physical chemistry. B · 2024Article
- Article
- Cellular Lipids Regulate the Conformational Ensembles of the Disordered Intracellular Loop 3 in β2 Adrenergic Receptor.bioRxiv : the preprint server for biology · 2023Article
- Global research trends of infantile hemangioma: A bibliometric and visualization analysis from 2000 to 2022.Heliyon · 2023Article
160 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
16 authors at 4 institutions in 4 countries.
Funding
Abstract
G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the beta(2) adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.
Indexed as
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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.