登録情報 データベース : EMDB / ID : EMD-35444 ダウンロードとリンクタイトル Cryo-EM structure of HCA2-Gi complex with LUF6283 マップデータmap 詳細 試料複合体 : Multiprotein complexタンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2タンパク質・ペプチド : Soluble cytochrome b562,Hydroxycarboxylic acid receptor 2タンパク質・ペプチド : scFv16リガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : 5-butyl-1~{H}-pyrazole-3-carboxylic acid 詳細 キーワード GPCR / SIGNALING PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
Activation of the phototransduction cascade / Olfactory Signaling Pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 ... Activation of the phototransduction cascade / Olfactory Signaling Pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thromboxane signalling through TP receptor / G beta:gamma signalling through BTK / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (s) signalling events / Ca2+ pathway / G-protein activation / Extra-nuclear estrogen signaling / G alpha (12/13) signalling events / neutrophil apoptotic process / nicotinic acid receptor activity / G alpha (q) signalling events / Hydroxycarboxylic acid-binding receptors / Vasopressin regulates renal water homeostasis via Aquaporins / GPER1 signaling / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / ADP signalling through P2Y purinoceptor 1 / G alpha (i) signalling events / positive regulation of neutrophil apoptotic process / Class A/1 (Rhodopsin-like receptors) / positive regulation of adiponectin secretion / photoreceptor outer segment membrane / spectrin binding / alkylglycerophosphoethanolamine phosphodiesterase activity / phototransduction, visible light / photoreceptor outer segment / negative regulation of lipid catabolic process / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / cardiac muscle cell apoptotic process / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / photoreceptor inner segment / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / electron transport chain / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / GDP binding / cell junction / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / ADORA2B mediated anti-inflammatory cytokines production / myelin sheath / GPER1 signaling / heterotrimeric G-protein complex / G-protein beta-subunit binding / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / sperm principal piece / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / GTPase binding / cell body / G protein activity / midbody / cell cortex / cellular response to hypoxia / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / periplasmic space / electron transfer activity / cell population proliferation / Extra-nuclear estrogen signaling / ciliary basal body / iron ion binding 類似検索 - 分子機能 : / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. ... : / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Soluble cytochrome b562 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Hydroxycarboxylic acid receptor 2 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.06 Å 詳細 データ登録者Suzuki S / Nishikawa K / Suzuki H / Fujiyoshi Y 資金援助 日本, 1件 詳細 詳細を隠すOrganization Grant number 国 Japan Society for the Promotion of Science (JSPS) 20H00451 日本
引用ジャーナル : Nat Commun / 年 : 2023タイトル : Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding.著者 : Shota Suzuki / Kotaro Tanaka / Kouki Nishikawa / Hiroshi Suzuki / Atsunori Oshima / Yoshinori Fujiyoshi / 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. 履歴 登録 2023年2月22日 - ヘッダ(付随情報) 公開 2023年8月30日 - マップ公開 2023年8月30日 - 更新 2025年7月2日 - 現状 2025年7月2日 処理サイト : PDBj / 状態 : 公開
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