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TitleStructures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes.
Journal, issue, pagesScience, Vol. 364, Issue 6440, Page 552-557, Year 2019
Publish dateMay 10, 2019
AuthorsShoji Maeda / Qianhui Qu / Michael J Robertson / Georgios Skiniotis / Brian K Kobilka /
PubMed AbstractMuscarinic 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 ...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.
External linksScience / PubMed:31073061 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.6 Å
Structure data

20078

6oij

EMDB-20078, PDB-6oij:
Muscarinic acetylcholine receptor 1-G11 protein complex
Method: EM (single particle) / Resolution: 3.3 Å

20079

6oik

EMDB-20079, PDB-6oik:
Muscarinic acetylcholine receptor 2-Go complex
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-IXO:
4-(4,5-dihydro-1,2-oxazol-3-yloxy)-N,N,N-trimethylbut-2-yn-1-aminium

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-2CU:
3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]thieno[2,3-b]pyridine-2-carboxamide

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsSIGNALING PROTEIN / G-protein coupled receptor-G-protein complex / neurotransmitter receptor

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