Structural highlights
Function
PE2R4_HUMAN Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.
Publication Abstract from PubMed
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 A. 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(2.39) and Trp327(7.51)). These findings may be important for the thorough understanding of the G protein-binding mechanism of EP4 and other prostanoid receptors.
Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein.,Nojima S, Fujita Y, Kimura KT, Nomura N, Suno R, Morimoto K, Yamamoto M, Noda T, Iwata S, Shigematsu H, Kobayashi T Structure. 2021 Mar 4;29(3):252-260.e6. doi: 10.1016/j.str.2020.11.007. Epub 2020 , Dec 1. PMID:33264604[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nojima S, Fujita Y, Kimura KT, Nomura N, Suno R, Morimoto K, Yamamoto M, Noda T, Iwata S, Shigematsu H, Kobayashi T. Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein. Structure. 2021 Mar 4;29(3):252-260.e6. PMID:33264604 doi:10.1016/j.str.2020.11.007
