9LRB

Cryo-EM structure of the histamine H1 receptor-Gs protein complex

9LRB の概要

• エントリーDOI: 10.2210/pdb9lrb/pdb
• EMDBエントリー: 63324
• 分子名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: gpcr, class a gpcr, histamine, g protein, complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 180717.37

構造登録者

Matsuzaki, Y.,Sano, F.K.,Oshima, H.S.,Akasaka, H.,Kobayashi, K.,Tanaka, T.,Itoh, Y.,Shihoya, W.,Kise, Y.,Kusakizako, T.,Nureki, O. (登録日: 2025-01-30, 公開日: 2025-06-11, 最終更新日: 2025-07-23)

主引用文献

Matsuzaki, Y.,Sano, F.K.,Oshima, H.S.,Akasaka, H.,Kobayashi, K.,Tanaka, T.,Itoh, Y.,Shihoya, W.,Kise, Y.,Kusakizako, T.,Inoue, A.,Nureki, O.
Structural insights into ligand recognition and G protein preferences across histamine receptors.
Commun Biol, 8:957-957, 2025

PubMed Abstract: Histamine exerts critical physiological roles by activating four receptor subtypes, each exhibiting a specific G protein preference. Among these, the histamine H receptor (HR) modulates chemotaxis and interferon production through G protein activation, suggesting its therapeutic potential. Despite its physiological significance, the mechanisms underlying HR signalling and G protein preference across histamine receptors remain poorly understood. Here, we present the cryo-electron microscopy structure of the HR-G complex, revealing unique mechanisms of histamine recognition and receptor activation. We further solved the structures of the histamine H receptor (HR) bound to the non-canonical G proteins G and G. Through a combination of functional and computational analyses, we identified the intracellular loop 2 as a critical determinant of G protein preference in HR and HR. Collectively, our comprehensive study revealed the structural basis for distinct mechanisms of ligand recognition and receptor activation, offering a profound insight into G protein preference across receptor subtypes.

PubMed: 40579541
DOI: 10.1038/s42003-025-08363-7

実験手法

ELECTRON MICROSCOPY (2.77 Å)