EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis of stepwise proton sensing-mediated GPCR activation.
ジャーナル・号・ページ	Cell Res, Vol. 35, Issue 6, Page 423-436, Year 2025
掲載日	2025年4月11日
著者	Xiaolei Yue / Li Peng / Shenhui Liu / Bingjie Zhang / Xiaodan Zhang / Hao Chang / Yuan Pei / Xiaoting Li / Junlin Liu / Wenqing Shui / Lijie Wu / Huji Xu / Zhi-Jie Liu / Tian Hua /
PubMed 要旨	The regulation of pH homeostasis is crucial in many biological processes vital for survival, growth, and function of life. The pH-sensing G protein-coupled receptors (GPCRs), including GPR4, GPR65 ...The regulation of pH homeostasis is crucial in many biological processes vital for survival, growth, and function of life. The pH-sensing G protein-coupled receptors (GPCRs), including GPR4, GPR65 and GPR68, play a pivotal role in detecting changes in extracellular proton concentrations, impacting both physiological and pathological states. However, comprehensive understanding of the proton sensing mechanism is still elusive. Here, we determined the cryo-electron microscopy structures of GPR4 and GPR65 in various activation states across different pH levels, coupled with G, G or G proteins, as well as a small molecule NE52-QQ57-bound inactive GPR4 structure. These structures reveal the dynamic nature of the extracellular loop 2 and its signature conformations in different receptor states, and disclose the proton sensing mechanism mediated by networks of extracellular histidine and carboxylic acid residues. Notably, we unexpectedly captured partially active intermediate states of both GPR4-G and GPR4-G complexes, and identified a unique allosteric binding site for NE52-QQ57 in GPR4. By integrating prior investigations with our structural analysis and mutagenesis data, we propose a detailed atomic model for stepwise proton sensation and GPCR activation. These insights may pave the way for the development of selective ligands and targeted therapeutic interventions for pH sensing-relevant diseases.
リンク	Cell Res / PubMed:40211064 / PubMed Central
手法	EM (単粒子)
解像度	2.67 - 3.35 Å
構造データ	39927 8zce EMDB-39927, PDB-8zce: Cryo-EM structure of GPR4 complexed with Gs in pH6.0 手法: EM (単粒子) / 解像度: 3.1 Å 39928 8zcf EMDB-39928, PDB-8zcf: Cryo-EM structure of GPR4 complexed with Gs in pH7.5 手法: EM (単粒子) / 解像度: 2.9 Å 61439 9jft EMDB-61439, PDB-9jft: Cryo-EM structure of GPR65 complexed with miniGs in pH6.5 手法: EM (単粒子) / 解像度: 3.27 Å 61440 9jfu EMDB-61440, PDB-9jfu: Cryo-EM structure of inactive GPR4 with NE52-QQ57 手法: EM (単粒子) / 解像度: 3.23 Å 61441 9jfv EMDB-61441, PDB-9jfv: Cryo-EM structure of GPR4 complexed with miniGs/q in pH6.8 手法: EM (単粒子) / 解像度: 2.67 Å 61442 9jfw EMDB-61442, PDB-9jfw: Cryo-EM structure of GPR4 complexed with Gs in pH6.8 手法: EM (単粒子) / 解像度: 3.13 Å 61443 9jfx EMDB-61443, PDB-9jfx: Cryo-EM structure of GPR4 complexed with miniGs/q in pH7.5 手法: EM (単粒子) / 解像度: 2.87 Å 61445 9jfz EMDB-61445, PDB-9jfz: Cryo-EM structure of intermediate state GPR4 complexed with miniGs/q in pH7.5 手法: EM (単粒子) / 解像度: 2.9 Å 61489 9jhp EMDB-61489, PDB-9jhp: Cryo-EM structure of GPR4 complexed with miniG13 in pH6.8 手法: EM (単粒子) / 解像度: 3.35 Å 63068 9lgm EMDB-63068, PDB-9lgm: Cryo-EM structure of GPR4 complexed with Gs in pH8.0 手法: EM (単粒子) / 解像度: 2.84 Å
化合物	PDB-1l1e: Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine
由来	homo sapiens (ヒト) lama glama (ラマ) Escherichia coli (大腸菌)
キーワード	SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / GPR4 / DNGs / Proton sensing / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex / GPR65 / miniGs / Gs / Gsq / G Protein / miniG13