9.A.14.3.2
The muscarinic acetylcholine G-protein-coupled receptor (Jo et al., 2010). Endothelial-dependent muscarinic receptor signaling acts largely through TRPV4 sparklet-mediated stimulation of IK (1.A.1.16.2) and SK (1.A.1.16.1) channels to promote vasodilation. There are five muscarinic receptor subtypes (M1R to M5R), which, despite sharing a high degree of sequence identity in the transmembrane region, couple to different heterotrimeric G proteins to transmit signals. M1R, M3R, and M5R couple to the G_{q/ 11} family, whereas M2R and M4R couple to the G_{i/ o} family. Maeda et al. 2019 presented and compared the cryo-electron microscopy structures of M1R in complex with G₁₁ and M2R in complex with G_oA. The M1R-G₁₁ complex exhibits distinct features, including an extended transmembrane helix 5 and carboxyl-terminal receptor tail that interacts with the G protein. Detailed analysis provides a framework for understanding the molecular determinants of G-protein coupling selectivity (Maeda et al. 2019).