ArticleProceedings of the National Academy of Sciences of the United States of America2012
Predicted structure of agonist-bound glucagon-like peptide 1 receptor, a class B G protein-coupled receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Glucagon-Like Peptide 1 (GLP-1) Receptor Variants and Glycemic Response to Liraglutide: A Pharmacogenetics Study in Iranian People with Type 2 Diabetes Mellitus.Advances in therapy · 2024 · on this mapTrial
- Methotrexate Inhibits the Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Receptor Binding Domain to the Host-Cell Angiotensin-Converting Enzyme-2 (ACE-2) Receptor.ACS pharmacology & translational science · 2024Article
- Targeting β Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats.ACS pharmacology & translational science · 2023Article
- Predicted structure and cell signaling of TAS2R14 reveal receptor hyper-flexibility for detecting diverse bitter tastes.iScience · 2023Article
- Association between glucagon-like peptide-1 receptor gene polymorphism and treatment response to GLP1R agonists in Chinese patients with type 2 diabetes: a prospective cohort study.European journal of clinical pharmacology · 2022Article
- Structures and Agonist Binding Sites of Bitter Taste Receptor TAS2R5 Complexed with Gi Protein and Validated against Experiment.The journal of physical chemistry letters · 2021Article
- Predicted structure of fully activated human bitter taste receptor TAS2R4 complexed with G protein and agonists.QRB discovery · 2021Article
- Advances in GLP-1 receptor targeting radiolabeled agent development and prospective of theranostics.Theranostics · 2020Review
- Exendin-4 analogs in insulinoma theranostics.Journal of labelled compounds & radiopharmaceuticals · 2019Review
- Article
- Cardiovascular Benefits of Native GLP-1 and its Metabolites: An Indicator for GLP-1-Therapy Strategies.Frontiers in physiology · 2017Review
- Conformational and Thermodynamic Landscape of GPCR Activation from Theory and Computation.Biophysical journal · 2016Article
- Structural insight into antibody-mediated antagonism of the Glucagon-like peptide-1 Receptor.Scientific reports · 2016Article
- Positive Allosteric Modulation of the Glucagon-like Peptide-1 Receptor by Diverse Electrophiles.The Journal of biological chemistry · 2016Article
- Article
- Ligand binding pocket formed by evolutionarily conserved residues in the glucagon-like peptide-1 (GLP-1) receptor core domain.The Journal of biological chemistry · 2015Article
- Targeting GLP-1 receptors for repeated magnetic resonance imaging differentiates graded losses of pancreatic beta cells in mice.Diabetologia · 2015Article
- Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.Nature communications · 2015Article
- Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes.Journal of diabetes research · 2015Article
- GLP-1 based therapeutics: simultaneously combating T2DM and obesity.Frontiers in neuroscience · 2015Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) involved in insulin synthesis and regulation; therefore, it is an important drug target for treatment of diabetes. However, GLP1R is a member of the class B1 family of GPCRs for which there are no experimental structures. To provide a structural basis for drug design and to probe class B GPCR activation, we predicted the transmembrane (TM) bundle structure of GLP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes) using the MembStruk method for scanning TM bundle conformations. We used protein-protein docking methods to combine the TM bundle with the X-ray crystal structure of the 143-aa N terminus coupled to the Exe4 peptide. This complex was subjected to 28 ns of full-solvent, full-lipid molecular dynamics. We find 14 strong polar interactions of Exe4 with GLP1R, of which 8 interactions are in the TM bundle (2 interactions confirmed by mutation studies) and 6 interactions involve the N terminus (3 interactions found in the crystal structure). We also find 10 important hydrophobic interactions, of which 4 interactions are in the TM bundle (2 interactions confirmed by mutation studies) and 6 interactions are in the N terminus (6 interactions present in the crystal structure). Thus, our predicted structure agrees with available mutagenesis studies. We suggest a number of mutation experiments to further validate our predicted structure. The structure should be useful for guiding drug design and can provide a structural basis for understanding ligand binding and receptor activation of GLP1R and other class B1 GPCRs.
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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.