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 hydroxycarboxylic acid receptor signaling mechanisms through ligand binding.
ジャーナル・号・ページ	Nat Commun, Vol. 14, Issue 1, Page 5899, Year 2023
掲載日	2023年9月22日
著者	Shota Suzuki / Kotaro Tanaka / Kouki Nishikawa / Hiroshi Suzuki / Atsunori Oshima / Yoshinori Fujiyoshi /
PubMed 要旨	Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only ...Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms.
リンク	Nat Commun / PubMed:37736747 / PubMed Central
手法	EM (単粒子)
解像度	2.85 - 3.21 Å
構造データ	35442 8ihb EMDB-35442, PDB-8ihb: Cryo-EM structure of HCA2-Gi complex with GSK256073 手法: EM (単粒子) / 解像度: 2.85 Å 35443 8ihf EMDB-35443, PDB-8ihf: Cryo-EM structure of HCA2-Gi complex with MK6892 手法: EM (単粒子) / 解像度: 2.97 Å 35444 8ihh EMDB-35444, PDB-8ihh: Cryo-EM structure of HCA2-Gi complex with LUF6283 手法: EM (単粒子) / 解像度: 3.06 Å 35445 8ihi EMDB-35445, PDB-8ihi: Cryo-EM structure of HCA2-Gi complex with acifran 手法: EM (単粒子) / 解像度: 3.11 Å 35446 8ihj EMDB-35446, PDB-8ihj: Cryo-EM structure of HCA3-Gi complex with acifran 手法: EM (単粒子) / 解像度: 3.07 Å 35447 8ihk EMDB-35447, PDB-8ihk: Cryo-EM structure of HCA3-Gi complex with acifran (local) 手法: EM (単粒子) / 解像度: 3.21 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-OKL: 8-chloranyl-3-pentyl-7H-purine-2,6-dione ChemComp-FI7: 2-[[2,2-dimethyl-3-[3-(5-oxidanylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]propanoyl]amino]cyclohexene-1-carboxylic acid ChemComp-P8A: 5-butyl-1~{H}-pyrazole-3-carboxylic acid ChemComp-P9X: (5~{S})-5-methyl-4-oxidanylidene-5-phenyl-furan-2-carboxylic acid
由来	homo sapiens (ヒト) synthetic construct (人工物) mus musculus (ハツカネズミ) escherichia coli (大腸菌)
キーワード	SIGNALING PROTEIN / GPCR (Gタンパク質共役受容体)