ArticleThe Journal of biological chemistry2016
Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R).
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 63 citations in OpenAlex.
- 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
- Neurobiological Mechanisms and Therapeutic Potential of Glucagon-like Peptide-1 Receptor Agonists in Binge Eating Disorder: A Narrative Review.International journal of molecular sciences · 2025Review
- Mapping Peptide-Protein Interactions by Amine-Reactive Cleavable Photoaffinity Reagents.ACS omega · 2023Article
- Investigating Potential GLP-1 Receptor Agonists in Cyclopeptides fromMetabolites · 2022Article
- Design, synthesis, and biological evaluation of a small molecule oral agonist of the glucagon-like-peptide-1 receptor.The Journal of biological chemistry · 2022Article
- Structural and functional diversity among agonist-bound states of the GLP-1 receptor.Nature chemical biology · 2022Article
- GLP-1 Val8: A Biased GLP-1R Agonist with Altered Binding Kinetics and Impaired Release of Pancreatic Hormones in Rats.ACS pharmacology & translational science · 2021Article
- A combined activation mechanism for the glucagon receptor.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Full-length human GLP-1 receptor structure without orthosteric ligands.Nature communications · 2020Article
- The Discovery and Development of Liraglutide and Semaglutide.Frontiers in endocrinology · 2019 · on this mapReview
- Molecular characterization of G-protein-coupled receptor (GPCR) and protein kinase A (PKA) cDNA inPeerJ · 2019Article
- Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex.Nature · 2018Article
- Polypharmacy through Phage Display: Selection of Glucagon and GLP-1 Receptor Co-agonists from a Phage-Displayed Peptide Library.Scientific reports · 2018Article
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- Thioamide Substitution Selectively Modulates Proteolysis and Receptor Activity of Therapeutic Peptide Hormones.Journal of the American Chemical Society · 2017Article
- Receptor activity-modifying protein dependent and independent activation mechanisms in the coupling of calcitonin gene-related peptide and adrenomedullin receptors to Gs.Biochemical pharmacology · 2017Article
- Article
- Article
- Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators.Nature · 2017Article
- High affinity binding of the peptide agonist TIP-39 to the parathyroid hormone 2 (PTHBiochemical pharmacology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
The glucagon-like peptide-1 receptor (GLP-1R) belongs to the secretin-like (class B) family of G protein-coupled receptors. Members of the class B family are distinguished by their large extracellular domain, which works cooperatively with the canonical seven-transmembrane (7TM) helical domain to signal in response to binding of various peptide hormones. We have combined structure-based site-specific mutational studies with molecular dynamics simulations of a full-length model of GLP-1R bound to multiple peptide ligand variants. Despite the high sequence similarity between GLP-1R and its closest structural homologue, the glucagon receptor (GCGR), nearly half of the 62 stably expressed mutants affected GLP-1R in a different manner than the corresponding mutants in GCGR. The molecular dynamics simulations of wild-type and mutant GLP-1R·ligand complexes provided molecular insights into GLP-1R-specific recognition mechanisms for the N terminus of GLP-1 by residues in the 7TM pocket and explained how glucagon-mimicking GLP-1 mutants restored binding affinity for (GCGR-mimicking) GLP-1R mutants. Structural analysis of the simulations suggested that peptide ligand binding mode variations in the 7TM binding pocket are facilitated by movement of the extracellular domain relative to the 7TM bundle. These differences in binding modes may account for the pharmacological differences between GLP-1 peptide variants.
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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.