PXD042562-1

PXD042562 is an original dataset announced via ProteomeXchange.

Title	Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq
Description	Muscarinic acetylcholine receptor M3 (M3) and its downstream effector Gq/11 are critical drug development targets given their involvement in numerous physiological processes and diseases. Although a cryo-electron microscopy study previously defined the structure of the M3-miniGq complex, the lack of information on the intracellular loop 3 (ICL3) of M3 and α-helical domain (AHD) of Gαq has made it difficult to comprehend the molecular mechanism of M3-Gq coupling fully. Here, we present the molecular mechanism underlying the dynamic interactions between the wild-type full-length M3 and heterotrimeric Gq using hydrogen-deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cell systems. This study suggests potential binding interfaces between M3 and Gq in pre-assembled and fully active nucleotide-free complexes. In addition to well-known binding interfaces, we observed the interaction of long ICL3 with Gβγ. Furthermore, M3 ICL3 negatively affected M3-Gq coupling, and the Gαq AHD underwent unique conformational changes during M3-Gq coupling. Therefore, we propose a comprehensive molecular mechanism of M3-Gq coupling by analyzing previously well-defined binding interfaces and neglected regions, such as M3 ICL3 and the Gαq AHD.
HostingRepository	PRIDE
AnnounceDate	2024-05-22
AnnouncementXML	Submission_2024-05-22_05:48:08.869.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Donghee Ham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Xevo G2 Q-Tof; Xevo G2-XS QTof

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-30 21:23:21	ID requested
⏵ 1	2024-05-22 05:48:09	announced

Ham D, Inoue A, Xu J, Du Y, Chung KY, Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq. Commun Biol, 7(1):362(2024) [pubmed]

10.1038/s42003-024-06056-1;

submitter keyword: HDX-MS, M3, G protein, Gq, GPCR

Ka Young
contact affiliation	School of Pharmacy, Sungkyunkwan University, South Korea
contact email	kychung2@gmail.com
lab head
Donghee Ham
contact affiliation	School of Pharmacy, Sungkyunkwan University
contact email	geg94@naver.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042562
     1. Label: PRIDE project
     2. Name: Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq