Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq.
Commun Biol
; 7(1): 362, 2024 Mar 23.
Article
in En
| MEDLINE
| ID: mdl-38521872
ABSTRACT
Muscarinic acetylcholine receptor M3 (M3) and its downstream effector Gq/11 are critical drug development targets due to their involvement in physiopathological processes. Although the structure of the M3-miniGq complex was recently published, the lack of information on the intracellular loop 3 (ICL3) of M3 and extensive modification of Gαq impedes the elucidation of the molecular mechanism of M3-Gq coupling under more physiological condition. Here, we describe the molecular mechanism underlying the dynamic interactions between full-length wild-type M3 and Gq using hydrogen-deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cell systems. We propose a detailed analysis of M3-Gq coupling through examination of previously well-defined binding interfaces and neglected regions. Our findings suggest potential binding interfaces between M3 and Gq in pre-assembled and functionally active complexes. Furthermore, M3 ICL3 negatively affected M3-Gq coupling, and the Gαq AHD underwent unique conformational changes during M3-Gq coupling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Muscarinic
/
GTP-Binding Protein alpha Subunits, Gq-G11
Language:
En
Journal:
Commun Biol
Year:
2024
Document type:
Article
Country of publication:
Reino Unido