Molecular mechanism of fatty acid activation of FFAR1.
FFAR1
GPCR
cryoEM
fatty acid
insulin
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
30 05 2023
30 05 2023
Historique:
medline:
24
5
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
ppublish
Résumé
FFAR1 is a G-protein-coupled receptor (GPCR) that responds to circulating free fatty acids to enhance glucose-stimulated insulin secretion and release of incretin hormones. Due to the glucose-lowering effect of FFAR1 activation, potent agonists for this receptor have been developed for the treatment of diabetes. Previous structural and biochemical studies of FFAR1 showed multiple sites of ligand binding to the inactive state but left the mechanism of fatty acid interaction and receptor activation unknown. We used cryo-electron microscopy to elucidate structures of activated FFAR1 bound to a G
Identifiants
pubmed: 37216523
doi: 10.1073/pnas.2219569120
pmc: PMC10235965
doi:
Substances chimiques
Insulin
0
Fatty Acids
0
Ligands
0
Receptors, G-Protein-Coupled
0
Fatty Acids, Nonesterified
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2219569120Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM131687
Pays : United States
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