Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein.
EP4
GPCR
GPCR-G protein complex
cryo-EM
prostaglandin E receptor
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
04 03 2021
04 03 2021
Historique:
received:
07
10
2020
revised:
27
10
2020
accepted:
06
11
2020
pubmed:
3
12
2020
medline:
25
11
2021
entrez:
2
12
2020
Statut:
ppublish
Résumé
Prostaglandin E receptor EP4, a class A G protein-coupled receptor (GPCR), is a common drug target in various disorders, such as acute decompensated heart failure and ulcerative colitis. Here, we report the cryoelectron microscopy (cryo-EM) structure of the EP4-heterotrimeric G protein (Gs) complex with the endogenous ligand at a global resolution of 3.3 Å. In this structure, compared with that in the inactive EP4 structure, the sixth transmembrane domain is shifted outward on the intracellular side, although the shift is smaller than that in other class A GPCRs bound to Gs. Instead, the C-terminal helix of Gs is inserted toward TM2 of EP4, and the conserved C-terminal hook structure formsthe extended state. These structural features are formed by the conserved residues in prostanoid receptors (Phe54
Identifiants
pubmed: 33264604
pii: S0969-2126(20)30419-6
doi: 10.1016/j.str.2020.11.007
pii:
doi:
Substances chimiques
Receptors, Prostaglandin E, EP4 Subtype
0
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
252-260.e6Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.