Fig. 1
1H, 13C HMQC spectra of ligand-bound methyl 13C-Met β1AR-MetΔ5-L190M show resonance positions that correlate with ligand efficacies. Chemical shift changes for 2D 1H, 13C HMQC spectra for [13C-methyl-Met] β1AR shown for the apo form (blue) and orthosteric ligands in order of efficacy (h); 7-methylcyanopindolol (very weak partial agonist, orange), carvedilol (weak partial agonist, red), cyanopindolol (weak partial agonist, green), salbutamol (partial agonist, purple) and isoprenaline (full agonist, pink). The crystal structure of β1AR (PDB code 4BVN) is shown in b with methionine residues used in this study shown as red spheres. The various methionines are shown separately; a M90, c M153, e M223, d M283, i M296. The centres of the resonances are indicated by coloured dots. Correlations between ligand efficacy and a linear combination of the chemical shifts (\({\mathrm{a}}\delta _{1_{\mathrm{H}}} + {\mathrm{b}}\delta _{13_{\mathrm{C}}} + {\mathrm{c}}\)) are shown in f and g with M223 fit to \(- 1045.1\delta _{1_{\mathrm{H}}} - 111.0\delta _{13_{\mathrm{C}}} + 3839.8\) and M296 to \(- 634.1\delta _{1_{\mathrm{H}}} - 239.9\delta _{13_{\mathrm{C}}} + 5614.1\). Full spectra are shown in Supplementary Fig. 3
