登録情報 データベース : EMDB / ID : EMD-30411 構造の表示 ダウンロードとリンクタイトル Dopamine Receptor D3R-Gi-PD128907 complex マップデータ 詳細 試料複合体 : Dopamine Receptor D3R-Gi-PD128907 complex複合体 : Guanine nucleotide-binding protein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複合体 : scFv16複合体 : chimera protein of Soluble cytochrome b562 and D(3) dopamine receptorタンパク質・ペプチド : Soluble cytochrome b562,D(3) dopamine receptorリガンド : (4aR,10bR)-4-propyl-3,4a,5,10b-tetrahydro-2H-chromeno[4,3-b][1,4]oxazin-9-ol 詳細 キーワード G protein-coupled receptor / Dopamine receptor / MEMBRANE 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
musculoskeletal movement, spinal reflex action / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / response to histamine / regulation of potassium ion transport / adenylate cyclase-inhibiting dopamine receptor signaling pathway / Dopamine receptors / regulation of dopamine uptake involved in synaptic transmission / positive regulation of dopamine receptor signaling pathway / phospholipase C-activating dopamine receptor signaling pathway ... musculoskeletal movement, spinal reflex action / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / response to histamine / regulation of potassium ion transport / adenylate cyclase-inhibiting dopamine receptor signaling pathway / Dopamine receptors / regulation of dopamine uptake involved in synaptic transmission / positive regulation of dopamine receptor signaling pathway / phospholipase C-activating dopamine receptor signaling pathway / negative regulation of oligodendrocyte differentiation / G protein-coupled receptor internalization / negative regulation of synaptic transmission, glutamatergic / response to morphine / arachidonate secretion / negative regulation of cytosolic calcium ion concentration / regulation of dopamine secretion / positive regulation of cytokinesis / dopamine metabolic process / social behavior / behavioral response to cocaine / negative regulation of protein secretion / prepulse inhibition / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / negative regulation of blood pressure / cellular response to forskolin / positive regulation of mitotic nuclear division / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of mitotic spindle organization / learning / locomotory behavior / Regulation of insulin secretion / circadian regulation of gene expression / response to cocaine / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / electron transport chain / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G protein-coupled receptor activity / visual learning / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / G-protein beta/gamma-subunit complex binding / centriolar satellite / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / intracellular calcium ion homeostasis / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / G protein activity / GTPase binding / retina development in camera-type eye / Ca2+ pathway / midbody / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events 類似検索 - 分子機能 Dopamine D3 receptor / Dopamine receptor family / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit ... Dopamine D3 receptor / Dopamine receptor family / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / 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 / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / 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 / D(3) dopamine receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) / Escherichia coli (大腸菌)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.7 Å 詳細 データ登録者Xu P / Huang S 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 2018YFA0507002 中国
引用ジャーナル : Mol Cell / 年 : 2021タイトル : Structures of the human dopamine D3 receptor-G complexes.著者: Peiyu Xu / Sijie Huang / Chunyou Mao / Brian E Krumm / X Edward Zhou / Yangxia Tan / Xi-Ping Huang / Yongfeng Liu / Dan-Dan Shen / Yi Jiang / Xuekui Yu / Hualiang Jiang / Karsten Melcher / ... 著者 : Peiyu Xu / Sijie Huang / Chunyou Mao / Brian E Krumm / X Edward Zhou / Yangxia Tan / Xi-Ping Huang / Yongfeng Liu / Dan-Dan Shen / Yi Jiang / Xuekui Yu / Hualiang Jiang / Karsten Melcher / Bryan L Roth / Xi Cheng / Yan Zhang / H Eric Xu / 要旨 : The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many ... The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders. Here, we report two cryo-EM structures of human D3R in complex with an inhibitory G protein and bound to the D3R-selective agonists PD128907 and pramipexole, the latter of which is used to treat patients with Parkinson's disease. The structures reveal agonist binding modes distinct from the antagonist-bound D3R structure and conformational signatures for ligand-induced receptor activation. Mutagenesis and homology modeling illuminate determinants of ligand specificity across dopamine receptors and the mechanisms for G protein coupling. Collectively our work reveals the basis of agonist binding and ligand-induced receptor activation and provides structural templates for designing specific ligands to treat CNS diseases targeting the dopaminergic system. 履歴 登録 2020年7月29日 - ヘッダ(付随情報) 公開 2021年3月10日 - マップ公開 2021年3月10日 - 更新 2024年10月16日 - 現状 2024年10月16日 処理サイト : PDBj / 状態 : 公開
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