Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein.
Structure
; 29(3): 252-260.e6, 2021 03 04.
Article
em En
| MEDLINE
| ID: mdl-33264604
ABSTRACT
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 (Phe542.39 and Trp3277.51). These findings may be important for the thorough understanding of the G protein-binding mechanism of EP4 and other prostanoid receptors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao GTP
/
Receptores de Prostaglandina E Subtipo EP4
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Structure
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão