Structures of the M1 and M2 Muscarinic Acetylcholine Receptor/G-protein Complexes

Overview

Journal Science

Specialty Science

Date 2019 May 11

PMID 31073061

Citations 157

Authors

Shoji Maeda

Qianhui Qu

Michael J Robertson

Georgios Skiniotis

Brian K Kobilka

Affiliations

Soon will be listed here.

Abstract

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 family, whereas M2R and M4R couple to the G family. Here, we present and compare the cryo-electron microscopy structures of M1R in complex with G and M2R in complex with G The M1R-G 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.

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