PXD042562 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-30 21:23:21 | ID requested | |
⏵ 1 | 2024-05-22 05:48:09 | announced | |
Publication List
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; |
Keyword List
submitter keyword: HDX-MS, M3, G protein, Gq, GPCR |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042562
- Label: PRIDE project
- Name: Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq