Fig. 3: Potential cryo-EM density for ML380.
From: Cryo-EM reveals an extrahelical allosteric binding site at the M5 mAChR
a–c Local refined M5 mAChR cryo-EM map (contour level 0.3). No ML380 density was observed in a ECV or b EH4 pocket. c Potential ML380 density observed parallel to TM1/TM7 (green) and the bottom of the TM2,3,4 interface (orange). d [3H]-NMS equilibrium binding studies between [3H]-NMS, ACh and ML380 at WT M5 mAChR and M5-M2 TM chimeras. Insets show receptor cartoons (blue: M5 domains; red: M2 domains). Data points are mean ± SEM values of three duplicate experiments. An allosteric ternary complex model was fit to the data. Parameters obtained are listed in Supplementary Table 3. RMSDs (Å) of e iperoxo in orthosteric pocket and f ML380 at the potential allosteric site at the bottom of the TM2,3,4 interface from GaMD simulations of the cryo-EM structure. Three simulation replicates are shown in different colours. Source data are provided as a Source Data file.
