ArticleNature2018
Structure of the glucagon receptor in complex with a glucagon analogue.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 140 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Potent and biased agonists of class B1 GPCRs from a heterochiral design strategy.Nature chemistry · 2026Article
- Conformational determinants of glucagon stability and aggregation kinetics in aqueous and commercial formulations.Protein science : a publication of the Protein Society · 2026Article
- Advances in Cyclic Peptides Targeting G Protein-Coupled Receptors.Chembiochem : a European journal of chemical biology · 2026Review
- Discovery of Biased Dual-Agonists of Glucagon-Like Peptide 1 and Glucagon Receptors through Mutation of a Conserved Aspartate.ACS medicinal chemistry letters · 2026Article
- Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens.Nature communications · 2026Article
- In Vitro Characterization of Agonist and Antagonist Peptide Binding Interaction Kinetics to GLP-1R in HEK293T Cells Using Surface Plasmon Resonance Microscopy.ACS medicinal chemistry letters · 2026Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence.Biophysical reviews · 2026Review
- Engineering a Glucose-Responsive Glucagon Prodrug Through Arginine-Phenylboronic Acid Pendant Modification.Small science · 2026Article
- Sequence constraints predispose Class D GPCRs to follow an atypical activation mechanism.bioRxiv : the preprint server for biology · 2026Article
- All roads lead to Rome: Emergence of Mechanistic Divergence Shapes Activation of Class B1 G-Protein Coupled Receptors.bioRxiv : the preprint server for biology · 2026Article
- Specific Glucagon Assay System Using a Receptor-Derived Glucagon-Binding Peptide Probe.International journal of molecular sciences · 2026Article
- The thyrotropin receptor structure and interactions with autoantibodies.European thyroid journal · 2025Review
- Advancing drug development with "Fit-for-Purpose" modeling informed approaches.Journal of pharmacokinetics and pharmacodynamics · 2025Review
- Ultrastable Insulin-Glucagon Fusion Protein Exploits an Endogenous Hepatic Switch to Mitigate Hypoglycemic Risk.ACS pharmacology & translational science · 2025Article
- Single-Molecule Insights into GPCR Conformational Landscapes.The Journal of membrane biology · 2025Review
- Advances in cryo-electron microscopy (cryoEM) for structure-based drug discovery.Expert opinion on drug discovery · 2025Review
- A Glucose-Responsive Glucagon-Micelle for the Prevention of Hypoglycemia.ACS central science · 2024Article
- Insights into the structure and activation mechanism of some class B1 GPCR family members.Molecular biology reports · 2024Review
22 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
22 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Class B G-protein-coupled receptors (GPCRs), which consist of an extracellular domain (ECD) and a transmembrane domain (TMD), respond to secretin peptides to play a key part in hormonal homeostasis, and are important therapeutic targets for a variety of diseases. Previous work has suggested that peptide ligands bind to class B GPCRs according to a two-domain binding model, in which the C-terminal region of the peptide targets the ECD and the N-terminal region of the peptide binds to the TMD binding pocket. Recently, three structures of class B GPCRs in complex with peptide ligands have been solved. These structures provide essential insights into peptide ligand recognition by class B GPCRs. However, owing to resolution limitations, the specific molecular interactions for peptide binding to class B GPCRs remain ambiguous. Moreover, these previously solved structures have different ECD conformations relative to the TMD, which introduces questions regarding inter-domain conformational flexibility and the changes required for receptor activation. Here we report the 3.0 Å-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702. This structure provides molecular details of the interactions between GCGR and the peptide ligand. It reveals a marked change in the relative orientation between the ECD and TMD of GCGR compared to the previously solved structure of the inactive GCGR-NNC0640-mAb1 complex. Notably, the stalk region and the first extracellular loop undergo major conformational changes in secondary structure during peptide binding, forming key interactions with the peptide. We further propose a dual-binding-site trigger model for GCGR activation-which requires conformational changes of the stalk, first extracellular loop and TMD-that extends our understanding of the previously established two-domain peptide-binding model of class B GPCRs.
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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.