Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes

Science. 2019 May 10;364(6440):552-557. doi: 10.1126/science.aaw5188.


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 Gq/ 11 family, whereas M2R and M4R couple to the Gi/ o family. Here, we present and compare the cryo-electron microscopy structures of M1R in complex with G11 and M2R in complex with GoA The M1R-G11 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cryoelectron Microscopy
  • GTP-Binding Protein alpha Subunits, Gi-Go / chemistry*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / chemistry*
  • Protein Multimerization
  • Protein Structure, Secondary
  • Receptor, Muscarinic M1 / chemistry*
  • Receptor, Muscarinic M2 / chemistry*


  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M2
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gq-G11