7YFD

Cryo-EM structure of the imetit-bound histamine H4 receptor and Gq complex

7YFD の概要

• エントリーDOI: 10.2210/pdb7yfd/pdb
• EMDBエントリー: 33786
• 分子名称: Engineered G-alpha-q, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (8 entities in total)
• 機能のキーワード: gpcr, aminergic receptor, histamine receptor, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 196750.47

構造登録者

Im, D.,Iwata, S.,Asada, H. (登録日: 2022-07-08, 公開日: 2023-10-25, 最終更新日: 2024-10-16)

主引用文献

Im, D.,Kishikawa, J.I.,Shiimura, Y.,Hisano, H.,Ito, A.,Fujita-Fujiharu, Y.,Sugita, Y.,Noda, T.,Kato, T.,Asada, H.,Iwata, S.
Structural insights into the agonists binding and receptor selectivity of human histamine H 4 receptor.
Nat Commun, 14:6538-6538, 2023

PubMed Abstract: Histamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H receptor (HR) 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 HR-G 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, which, in turn, form the "aromatic slot". The results provide insights into the molecular underpinnings of the agonism of HR and subtype selectivity of histamine receptors, and show that the HR structures may be valuable in rational drug design of drugs targeting the HR.

PubMed: 37863901
DOI: 10.1038/s41467-023-42260-z

実験手法

ELECTRON MICROSCOPY (3.1 Å)