Structural mechanism underlying primary and secondary coupling between GPCRs and the Gi/o family

Hee Ryung Kim, Jun Xu, Shoji Maeda, Nguyen Minh Duc, Donghoon Ahn, Yang Du () and Ka Young Chung ()
Additional contact information
Hee Ryung Kim: School of Pharmacy, Sungkyunkwan University
Jun Xu: Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University
Shoji Maeda: Stanford University
Nguyen Minh Duc: School of Pharmacy, Sungkyunkwan University
Donghoon Ahn: School of Pharmacy, Sungkyunkwan University
Yang Du: School of Life and Health Sciences, Kobilka Institute of Innovative Drug Discovery, Chinese University of Hong Kong
Ka Young Chung: School of Pharmacy, Sungkyunkwan University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Heterotrimeric G proteins are categorized into four main families based on their function and sequence, Gs, Gi/o, Gq/11, and G12/13. One receptor can couple to more than one G protein subtype, and the coupling efficiency varies depending on the GPCR-G protein pair. However, the precise mechanism underlying different coupling efficiencies is unknown. Here, we study the structural mechanism underlying primary and secondary Gi/o coupling, using the muscarinic acetylcholine receptor type 2 (M2R) as the primary Gi/o-coupling receptor and the β2-adrenergic receptor (β2AR, which primarily couples to Gs) as the secondary Gi/o-coupling receptor. Hydrogen/deuterium exchange mass spectrometry and mutagenesis studies reveal that the engagement of the distal C-terminus of Gαi/o with the receptor differentiates primary and secondary Gi/o couplings. This study suggests that the conserved hydrophobic residue within the intracellular loop 2 of the receptor (residue 34.51) is not critical for primary Gi/o-coupling; however, it might be important for secondary Gi/o-coupling.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16975-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16975-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16975-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().