Ligand-specific activation trajectories dictate GPCR signalling in cells.

ABSTRACT: G-protein-coupled receptors (GPCRs) are key mediators of cell communication and represent the most important class of drug targets^1,2. 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^3-11. However, how efficacy is encoded and whether multiple receptor states occur in living cells remain unclear. Here we use genetic code expansion¹² and bioorthogonal labelling^13-16 to generate a panel of fluorescence-based biosensors for a prototypical GPCR, the M₂ muscarinic acetylcholine receptor (M₂R). These biosensors enable real-time monitoring of agonist-promoted conformational changes ac

SUBMITTER: Thomas R 

PROVIDER: S-EPMC12935549 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature