News Releases & Research Results Structural analysis of a G protein-coupled prostaglandin receptor, leading to the elucidation of the EP4 activation mechanism - Promising findings for the development of therapeutic methods for ulcerative colitis, acute heart failure, osteoporosis, glomerulonephritis, etc. -

The results of research conducted by Professor Takuya Shimizu (Kobayashi) of the Department of Medical Chemistry, Kansai Medical University, Professor So Iwata and Graduate student Shingo Nojima of the Department of Cell Biology, Graduate School of Medicine, Kyoto University, Professor Takeshi Noda and Graduate student Yoko Fujita of the Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University and Director Masaki Yamamoto and Researcher Hideki Shigematsu of the RIKEN SPring-8 Center Advanced Photon Technology Division.

• The complex of prostaglandin (PGE2)-bound prostaglandin receptor (EP4) and G protein was purified and analyzed, leading to the elucidation of its structure and activation mechanism for the first time in the world.
• EP4 agonists should serve as therapeutics for ulcerative colitis and acute heart failure. The elucidation of the activation mechanism of EP4 should facilitate the development of novel therapeutics for these diseases.

This project was conducted with the support of the Research on Development of New Drugs by AMED.

The results were published in the American scientific journal Structure on December 2.

Nojima S., et al. Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein Structure
DOI: 10.1016/j.str.2020.11.007