{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["650(8103)"],"submitter":["Thomas R"],"pubmed_abstract":["G-protein-coupled receptors (GPCRs) are key mediators of cell communication and represent the most important class of drug targets<sup>1,2</sup>. Biophysical studies with purified GPCRs in vitro have suggested that they exist in an equilibrium of distinct inactive and active states, which is modulated by ligands in an efficacy-dependent manner<sup>3-11</sup>. However, how efficacy is encoded and whether multiple receptor states occur in living cells remain unclear. Here we use genetic code expansion<sup>12</sup> and bioorthogonal labelling<sup>13-16</sup> to generate a panel of fluorescence-based biosensors for a prototypical GPCR, the M<sub>2</sub> muscarinic acetylcholine receptor (M<sub>2</sub>R). These biosensors enable real-time monitoring of agonist-promoted conformational changes ac"],"journal":["Nature"],"pagination":["1053-1062"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12935549"],"repository":["biostudies-literature"],"pubmed_title":["Ligand-specific activation trajectories dictate GPCR signalling in cells."],"pmcid":["PMC12935549"],"pubmed_authors":["Jacoby PS","Staubert C","Lohse MJ","Thomas R","De Faveri C","Coin I","Liebing AD","Melkes B","Bermudez M","Bock A","Martini HJ","Derieux C"],"additional_accession":[]},"is_claimable":false,"name":"Ligand-specific activation trajectories dictate GPCR signalling in cells.","description":"G-protein-coupled receptors (GPCRs) are key mediators of cell communication and represent the most important class of drug targets<sup>1,2</sup>. Biophysical studies with purified GPCRs in vitro have suggested that they exist in an equilibrium of distinct inactive and active states, which is modulated by ligands in an efficacy-dependent manner<sup>3-11</sup>. However, how efficacy is encoded and whether multiple receptor states occur in living cells remain unclear. Here we use genetic code expansion<sup>12</sup> and bioorthogonal labelling<sup>13-16</sup> to generate a panel of fluorescence-based biosensors for a prototypical GPCR, the M<sub>2</sub> muscarinic acetylcholine receptor (M<sub>2</sub>R). These biosensors enable real-time monitoring of agonist-promoted conformational changes ac","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-16T21:58:54.314Z","creation":"2026-07-11T03:09:04.628Z"},"accession":"S-EPMC12935549","cross_references":{"pubmed":["41535472"],"doi":["10.1038/s41586-025-09963-3"]}}