8WW2

GPR3/Gs complex

8WW2 の概要

• エントリーDOI: 10.2210/pdb8ww2/pdb
• EMDBエントリー: 37881
• 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, ... (9 entities in total)
• 機能のキーワード: gpcr-g-protein complex, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 141785.80

構造登録者

He, Y.,Xiong, Y. (登録日: 2023-10-24, 公開日: 2024-02-14, 最終更新日: 2025-07-02)

主引用文献

Xiong, Y.,Xu, Z.,Li, X.,Wang, Y.,Zhao, J.,Wang, N.,Duan, Y.,Xia, R.,Han, Z.,Qian, Y.,Liang, J.,Zhang, A.,Guo, C.,Inoue, A.,Xia, Y.,Chen, Z.,He, Y.
Identification of oleic acid as an endogenous ligand of GPR3.
Cell Res., 34:232-244, 2024

PubMed Abstract: Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by combining structural approach (including cryo-electron microscopy), mass spectrometry analysis, and functional studies, we identify oleic acid (OA) as an endogenous ligand of GPR3. Our study reveals a hydrophobic tunnel within GPR3 that connects the extracellular side of the receptor to the middle of plasma membrane, enabling fatty acids to readily engage the receptor. Functional studies demonstrate that OA triggers downstream G signaling, whereas lysophospholipids fail to activate the receptor. Moreover, our research reveals that cold stimulation induces the secretion of OA in mice, subsequently activating G/cAMP/PKA signaling in brown adipose tissue. Notably, brown adipose tissues from Gpr3 knockout mice do not respond to OA during cold stimulation, reinforcing the significance of GPR3 in this process. Finally, we propose a "born to be activated and cold to enhance" model for GPR3 activation. Our study provides a starting framework for the understanding of GPR3 signaling in cold-stimulated thermogenesis.

PubMed: 38287117
DOI: 10.1038/s41422-024-00932-5

実験手法

ELECTRON MICROSCOPY (2.79 Å)