Crystal structure of the endogenous agonist-bound prostanoid receptor EP3

Kazushi Morimoto; Ryoji Suno; Yunhong Hotta; Keitaro Yamashita; Kunio Hirata; Masaki Yamamoto; Shuh Narumiya; So Iwata; Takuya Kobayashi

doi:10.1038/s41589-018-0171-8

Crystal structure of the endogenous agonist-bound prostanoid receptor EP3

Nat Chem Biol. 2019 Jan;15(1):8-10. doi: 10.1038/s41589-018-0171-8. Epub 2018 Dec 3.

Authors

Kazushi Morimoto^{1

2}, Ryoji Suno^{3

4}, Yunhong Hotta³, Keitaro Yamashita⁵, Kunio Hirata⁵, Masaki Yamamoto⁵, Shuh Narumiya⁶, So Iwata⁷, Takuya Kobayashi^{8

9

10}

Affiliations

¹ Department of Cell Biology, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, Japan. k.morimoto@mfour.med.kyoto-u.ac.jp.
² Japan Agency for Medical Research and Development (AMED), Core Research for Evolutional Science and Technology (CREST), Chiyoda-ku, Tokyo, Japan. k.morimoto@mfour.med.kyoto-u.ac.jp.
³ Department of Cell Biology, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, Japan.
⁴ Japan Agency for Medical Research and Development (AMED), Core Research for Evolutional Science and Technology (CREST), Chiyoda-ku, Tokyo, Japan.
⁵ RIKEN SPring-8 Center, Sayo-cho, Sayo-gun, Hyogo, Japan.
⁶ Medical Innovation Center, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
⁷ Department of Cell Biology, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, Japan. s.iwata@mfour.med.kyoto-u.ac.jp.
⁸ Department of Cell Biology, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, Japan. kobayashi.takuya.4r@kyoto-u.ac.jp.
⁹ Japan Agency for Medical Research and Development (AMED), Core Research for Evolutional Science and Technology (CREST), Chiyoda-ku, Tokyo, Japan. kobayashi.takuya.4r@kyoto-u.ac.jp.
¹⁰ Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan. kobayashi.takuya.4r@kyoto-u.ac.jp.

PMID: 30510192
DOI: 10.1038/s41589-018-0171-8

Abstract

Prostanoids are a series of bioactive lipid metabolites that function in an autacoid manner via activation of cognate G-protein-coupled receptors (GPCRs). Here, we report the crystal structure of human prostaglandin (PG) E receptor subtype EP3 bound to endogenous ligand PGE₂ at 2.90 Å resolution. The structure reveals important insights into the activation mechanism of prostanoid receptors and provides a molecular basis for the binding modes of endogenous ligands.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Crystallography, X-Ray
Dinoprostone / chemistry
Dinoprostone / metabolism
Humans
Models, Molecular
Protein Conformation
Receptors, Prostaglandin E, EP3 Subtype / agonists*
Receptors, Prostaglandin E, EP3 Subtype / chemistry*
Receptors, Prostaglandin E, EP3 Subtype / genetics
Receptors, Prostaglandin E, EP3 Subtype / metabolism
Transforming Growth Factor alpha / metabolism

Substances

PTGER3 protein, human
Receptors, Prostaglandin E, EP3 Subtype
Transforming Growth Factor alpha
Dinoprostone