Conformational plasticity of ligand-bound and ternary GPCR complexes studied by F NMR of the β-adrenergic receptor.

G-protein-coupled receptors (GPCRs) are allosteric signaling proteins that transmit an extracellular stimulus across the cell membrane. Using F NMR and site-specific labelling, we investigate the response of the cytoplasmic region of transmembrane helices 6 and 7 of the β-adrenergic receptor to agonist stimulation and coupling to a G-protein-mimetic nanobody. Agonist binding shows the receptor in equilibrium between two inactive states and a pre-active form, increasingly populated with higher ligand efficacy.