7D7M

Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein

Summary for 7D7M

• Entry DOI: 10.2210/pdb7d7m/pdb
• EMDB information: 30608
• Descriptor: Prostaglandin E2 receptor EP4 subtype,Prostaglandin E2 receptor EP4 subtype, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: prostaglandin e receptor, ep4, gpcr, g protein, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 126590.26

Authors

Nojima, S.,Fujita, Y.,Kimura, T.K.,Nomura, N.,Suno, R.,Morimoto, K.,Yamamoto, M.,Noda, T.,Iwata, S.,Shigematsu, H.,Kobayashi, T. (deposition date: 2020-10-05, release date: 2020-11-18, Last modification date: 2024-10-23)

Primary citation

Nojima, S.,Fujita, Y.,Kimura, K.T.,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, 29:252-260.e6, 2021

PubMed 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 (Phe54 and Trp327). These findings may be important for the thorough understanding of the G protein-binding mechanism of EP4 and other prostanoid receptors.

PubMed: 33264604
DOI: 10.1016/j.str.2020.11.007

Experimental method

ELECTRON MICROSCOPY (3.3 Å)