Assembly of a GPCR-G Protein Complex.
G protein
G protein-coupled receptor
conformation
dynamics
hydrogen/deuterium exchange mass spectrometry
hydroxyl radical footprinting mass spectrometry
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
16 05 2019
16 05 2019
Historique:
received:
03
10
2018
revised:
25
02
2019
accepted:
09
04
2019
pubmed:
14
5
2019
medline:
12
2
2020
entrez:
14
5
2019
Statut:
ppublish
Résumé
The activation of G proteins by G protein-coupled receptors (GPCRs) underlies the majority of transmembrane signaling by hormones and neurotransmitters. Recent structures of GPCR-G protein complexes obtained by crystallography and cryoelectron microscopy (cryo-EM) reveal similar interactions between GPCRs and the alpha subunit of different G protein isoforms. While some G protein subtype-specific differences are observed, there is no clear structural explanation for G protein subtype-selectivity. All of these complexes are stabilized in the nucleotide-free state, a condition that does not exist in living cells. In an effort to better understand the structural basis of coupling specificity, we used time-resolved structural mass spectrometry techniques to investigate GPCR-G protein complex formation and G-protein activation. Our results suggest that coupling specificity is determined by one or more transient intermediate states that serve as selectivity filters and precede the formation of the stable nucleotide-free GPCR-G protein complexes observed in crystal and cryo-EM structures.
Identifiants
pubmed: 31080064
pii: S0092-8674(19)30441-6
doi: 10.1016/j.cell.2019.04.022
pmc: PMC6763313
mid: NIHMS1528117
pii:
doi:
Substances chimiques
Multienzyme Complexes
0
Receptors, G-Protein-Coupled
0
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1232-1242.e11Subventions
Organisme : NCATS NIH HHS
ID : TL1 TR002549
Pays : United States
Organisme : NIH HHS
ID : S10 OD026882
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM083118
Pays : United States
Organisme : NIBIB NIH HHS
ID : P30 EB009998
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS028471
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007250
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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