{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Harikumar KG"],"funding":["NIDDK NIH HHS"],"pagination":["18607-12"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3494884"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["109(45)"],"pubmed_abstract":["The glucagon-like peptide-1 receptor (GLP-1R) is a family B G protein-coupled receptor and an important drug target for the treatment of type II diabetes, with activation of pancreatic GLP-1Rs eliciting glucose-dependent insulin secretion. Currently, approved therapeutics acting at this receptor are peptide based, and there is substantial interest in small molecule modulators for the GLP-1R. Using a variety of resonance energy transfer techniques, we demonstrate that the GLP-1R forms homodimers and that transmembrane helix 4 (TM4) provides the primary dimerization interface. We show that disruption of dimerization using a TM4 peptide, a minigene construct encoding TM4, or by mutation of TM4, eliminates G protein-dependent high-affinity binding to GLP-1(7-36)NH(2) but has selective effects "],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery."],"pmcid":["PMC3494884"],"funding_grant_id":["R01 DK046577","DK46577.","R56 DK046577"],"pubmed_authors":["Pinon DI","Sexton PM","Miller LJ","Graham B","Wootten D","Dong M","Ball AM","Koole C","Furness SG","Christopoulos A","Harikumar KG"],"additional_accession":[]},"is_claimable":false,"name":"Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery.","description":"The glucagon-like peptide-1 receptor (GLP-1R) is a family B G protein-coupled receptor and an important drug target for the treatment of type II diabetes, with activation of pancreatic GLP-1Rs eliciting glucose-dependent insulin secretion. Currently, approved therapeutics acting at this receptor are peptide based, and there is substantial interest in small molecule modulators for the GLP-1R. Using a variety of resonance energy transfer techniques, we demonstrate that the GLP-1R forms homodimers and that transmembrane helix 4 (TM4) provides the primary dimerization interface. We show that disruption of dimerization using a TM4 peptide, a minigene construct encoding TM4, or by mutation of TM4, eliminates G protein-dependent high-affinity binding to GLP-1(7-36)NH(2) but has selective effects ","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Nov","modification":"2025-04-04T10:11:35.689Z","creation":"2019-03-27T01:00:17Z"},"accession":"S-EPMC3494884","cross_references":{"pubmed":["23091034"],"doi":["10.1073/pnas.1205227109"]}}