Guanine nucleotide-binding protein subunit alpha-11
phospholipase C-activating G protein-coupled receptor signaling pathway
Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes.
Muscarinic acetylcholine receptors are G protein-coupled receptors that respond to acetylcholine and play important signaling roles in the nervous system. 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 GTP-binding proteins (G proteins) to transmit signals. M1R, M3R, and M5R couple to the G<sub>q/</sub> <sub>11</sub> family, whereas M2R and M4R couple to the G<sub>i/</sub> <sub>o</sub> family. Here, we present and compare the cryo-electron microscopy structures of M1R in complex with G<sub>11</sub> and M2R in complex with G<sub>oA</sub> The M1R-G<sub>11</sub> complex exhibits distinct features, including an extended transmembrane helix 5 and carboxyl-terminal receptor tail that interacts with G protein. Detailed analysis of these structures provides a framework for understanding the molecular determinants of G-protein coupling selectivity.