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TitleCryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein.
Journal, issue, pagesStructure, Vol. 29, Issue 3, Page 252-260.e6, Year 2021
Publish dateMar 4, 2021
AuthorsShingo Nojima / Yoko Fujita / Kanako Terakado Kimura / Norimichi Nomura / Ryoji Suno / Kazushi Morimoto / Masaki Yamamoto / Takeshi Noda / So Iwata / Hideki Shigematsu / Takuya Kobayashi /
PubMed AbstractProstaglandin 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 ...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 and Trp327). These findings may be important for the thorough understanding of the G protein-binding mechanism of EP4 and other prostanoid receptors.
External linksStructure / PubMed:33264604
MethodsEM (single particle)
Resolution3.3 Å
Structure data

30608

7d7m

EMDB-30608, PDB-7d7m:
Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-P2E:
(Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / medication*YM / Prostaglandin E2

Source
  • homo sapiens (human)
  • lama glama (llama)
KeywordsMEMBRANE PROTEIN / prostaglandin E receptor / EP4 / GPCR / G protein

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