7CX2

Cryo-EM structure of the PGE2-bound EP2-Gs complex

Summary for 7CX2

• Entry DOI: 10.2210/pdb7cx2/pdb
• EMDB information: 30489
• Descriptor: Prostaglandin E2 receptor EP2 subtype, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (7 entities in total)
• Functional Keywords: gpcr, ep2, complex, pge2, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 147072.07

Authors

Qu, C.,Mao, C.,Xiao, P.,Shen, Q.,Zhong, Y.,Yang, F.,Shen, D.,Tao, X.,Zhang, H.,Yan, X.,Zhao, R.,He, J.,Guan, Y.,Zhang, C.,Hou, G.,Zhang, P.,Yu, X.,Guan, Y.,Sun, J.,Zhang, Y. (deposition date: 2020-09-01, release date: 2021-05-05, Last modification date: 2024-11-06)

Primary citation

Qu, C.,Mao, C.,Xiao, P.,Shen, Q.,Zhong, Y.N.,Yang, F.,Shen, D.D.,Tao, X.,Zhang, H.,Yan, X.,Zhao, R.J.,He, J.,Guan, Y.,Zhang, C.,Hou, G.,Zhang, P.J.,Hou, G.,Li, Z.,Yu, X.,Chai, R.J.,Guan, Y.F.,Sun, J.P.,Zhang, Y.
Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E 2 receptor EP2 subtype.
Sci Adv, 7:-, 2021

PubMed Abstract: Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E (PGE) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo-electron microscopy structure of the EP2-G complex with its endogenous agonist PGE and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W "toggle switch" and coupling to G via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE signaling system.

PubMed: 33811074
DOI: 10.1126/sciadv.abf1268

Experimental method

ELECTRON MICROSCOPY (2.8 Å)