ArticleProceedings of the National Academy of Sciences of the United States of America2020
A combined activation mechanism for the glucagon receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- A Transferable and Robust Computational Framework for Class A GPCR Activation Free Energies.The journal of physical chemistry letters · 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
- Multiscale Simulation Approaches to Probe Lipid Interactions of G Protein-Coupled Receptors.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Enhanced Sampling and Tailored Collective Variables Yield Reproducible Free Energy Landscapes of Beta-1 Adrenergic Receptor Activation.Journal of chemical theory and computation · 2025Article
- Hidden GPCR structural transitions addressed by multiple walker supervised molecular dynamics (mwSuMD).eLife · 2025Article
- Leveraging Sequence Purification for Accurate Prediction of Multiple Conformational States with AlphaFold2.Research square · 2025Article
- A Glucose-Responsive Glucagon-Micelle for the Prevention of Hypoglycemia.ACS central science · 2024Article
- Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5.Nature communications · 2024Article
- The Inferential Binding Sites of GCGR for Small Molecules Using Protein Dynamic Conformations and Crystal Structures.International journal of molecular sciences · 2024Article
- Entropy drives the ligand recognition in G-protein-coupled receptor subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Uniform trehalose nanogels for glucagon stabilization.RSC applied polymers · 2024Article
- OneOPES, a Combined Enhanced Sampling Method to Rule Them All.Journal of chemical theory and computation · 2023Article
- Dynamic allosteric networks drive adenosine AeLife · 2023Article
- Computational Peptide Design Cotargeting Glucagon and Glucagon-like Peptide-1 Receptors.Journal of chemical information and modeling · 2023Article
- A versatile bioelectronic interface programmed for hormone sensing.Nature communications · 2023Article
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Unbinding Kinetics of Muscarinic M3 Receptor Antagonists Explained by Metadynamics Simulations.Journal of chemical information and modeling · 2023Article
- Activation mechanism of the human Smoothened receptor.Biophysical journal · 2023Article
- Mechanistic basis of GPCR activation explored by ensemble refinement of crystallographic structures.Protein science : a publication of the Protein Society · 2022Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report on a combined activation mechanism for a class B G-protein-coupled receptor (GPCR), the glucagon receptor. By computing the conformational free-energy landscape associated with the activation of the receptor-agonist complex and comparing it with that obtained with the ternary complex (receptor-agonist-G protein) we show that the agonist stabilizes the receptor in a preactivated complex, which is then fully activated upon binding of the G protein. The proposed mechanism contrasts with the generally assumed GPCR activation mechanism, which proceeds through an opening of the intracellular region allosterically elicited by the binding of the agonist. The mechanism found here is consistent with electron cryo-microscopy structural data and might be general for class B GPCRs. It also helps us to understand the mode of action of the numerous allosteric antagonists of this important drug target.
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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.