임도현 (Kyoto University)

한빛사논문

조회468

Kyoto University

CV File 171 kb

Nat. Commun., Oct 20 2023, 14 (1) 6538 | https://doi.org/10.1038/s41467-023-42260-z Structural insights into the agonists binding and receptor selectivity of human histamine H4 receptor

Dohyun Im ^1,9, Jun-ichi Kishikawa ^2,9, Yuki Shiimura ^1,3, Hiromi Hisano ¹, Akane Ito ¹, Yoko Fujita-Fujiharu ^4,5,6, Yukihiko Sugita ^4,5,7, Takeshi Noda ^4,5,6, Takayuki Kato ^2,*, Hidetsugu Asada ^1,* & So Iwata ^1,8,*

¹Department of Cell Biology, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
²Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
³Institute of Life Science, Kurume University, Kurume, Fukuoka 830-0011, Japan.
⁴Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
⁵Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
⁶CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
⁷Hakubi Center for Advanced Research, Kyoto University, Kyoto 606-8501, Japan.
⁸RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan.
⁹These authors contributed equally: Dohyun Im, Jun-ichi Kishikawa.

^*Corresponding authors: correspondence to Takayuki Kato, Hidetsugu Asada or So Iwata

Abstract

Histamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H₄ receptor (H₄R) is a potential therapeutic target for chronic inflammatory diseases such as asthma and atopic dermatitis. Here, we show the cryo-electron microscopy structures of the H₄R-G_q complex bound with an endogenous agonist histamine or the selective agonist imetit bound in the orthosteric binding pocket. The structures demonstrate binding mode of histamine agonists and that the subtype-selective agonist binding causes conformational changes in Phe344^7.39, which, in turn, form the "aromatic slot". The results provide insights into the molecular underpinnings of the agonism of H₄R and subtype selectivity of histamine receptors, and show that the H₄R structures may be valuable in rational drug design of drugs targeting the H₄R.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-10-25)
연구진국외 연구진
분야 생명과학 > 구조생물 및 생물물리학

댓글 작성 로그인

CV 열람하기

연락처 보기