Extended Data Figure 1. Thermo-stability of DRD2 constructs, crystal packing of the DRD2/Risperidone complex and representative electron density of the DRD2 structure.

a, DRD2 or thermo-stability mutation membrane with 1nM [³H]-N-methylspiperone were heated for 30 min, the amount of [³H]-ligand bound determined. b, Purified DRD2-T4L (with or without thermo-stability mutation) protein with 10 μM risperidone and 1 μM BODIPY FL L-cystine dye were heated by a temperature gradient and the amount of dye bound to unfolding protein determined. Data were analyzed by nonlinear regression and apparent Tm values (transition temperature where 50% of the receptor is inactive) were determined from analysis of the sigmoidal dose-response curves. All data in a-b are the mean $\pm$SEM of three independent assays. Error bars in a-b denote SEM from three independent assays. c, d, e, Packing of the DRD2/Risperidone complex crystallized in the P2₁2₁2₁ spacegroup. The DRD2 is shown in green and T4L fusion protein is shown in red or cyan (interact with DRD2). EL₁ and EL₂ of DRD2 were shown in magenta and blue, respectively. f, 2Fo-Fc electron density map (blue mesh) of risperidone (yellow) contoured at 1σ. g, Fo-Fc omit map (green mesh) contoured at 3.0σ of risperidone (yellow). h, 2Fo-Fc electron density map of DRD2 binding pocket residues (blue mesh) contoured at 1σ.