+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7jvp | |||||||||||||||
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タイトル | Cryo-EM structure of SKF-83959-bound dopamine receptor 1 in complex with Gs protein | |||||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN / Dopamine receptor 1 / Gi protein / SKF-83959 | |||||||||||||||
機能・相同性 | 機能・相同性情報 dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / sensitization / operant conditioning / Dopamine receptors / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / dopamine binding / heterotrimeric G-protein binding ...dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / sensitization / operant conditioning / Dopamine receptors / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / dopamine binding / heterotrimeric G-protein binding / G protein-coupled receptor complex / peristalsis / regulation of dopamine metabolic process / grooming behavior / phospholipase C-activating dopamine receptor signaling pathway / positive regulation of neuron migration / habituation / dopamine transport / positive regulation of potassium ion transport / astrocyte development / conditioned taste aversion / striatum development / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / long-term synaptic depression / mating behavior / adult walking behavior / ciliary membrane / G protein-coupled dopamine receptor signaling pathway / temperature homeostasis / D-glucose import / transmission of nerve impulse / dopamine metabolic process / PKA activation in glucagon signalling / behavioral response to cocaine / hair follicle placode formation / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / behavioral fear response / developmental growth / neuronal action potential / G-protein alpha-subunit binding / D1 dopamine receptor binding / intracellular transport / renal water homeostasis / Hedgehog 'off' state / prepulse inhibition / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / GABA-ergic synapse / cellular response to glucagon stimulus / synapse assembly / adenylate cyclase activator activity / presynaptic modulation of chemical synaptic transmission / response to amphetamine / regulation of insulin secretion / positive regulation of synaptic transmission, glutamatergic / positive regulation of release of sequestered calcium ion into cytosol / trans-Golgi network membrane / synaptic transmission, glutamatergic / long-term synaptic potentiation / G protein-coupled receptor activity / negative regulation of inflammatory response to antigenic stimulus / bone development / regulation of protein phosphorylation / visual learning / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / cilium / G protein-coupled acetylcholine receptor signaling pathway / G protein activity / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / memory / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / vasodilation / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / protein import into nucleus 類似検索 - 分子機能 | |||||||||||||||
生物種 | Homo sapiens (ヒト) synthetic construct (人工物) | |||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||||||||
データ登録者 | Zhuang, Y. / Xu, P. / Mao, C. / Wang, L. / Krumm, B. / Zhou, X.E. / Huang, S. / Liu, H. / Cheng, X. / Huang, X.-P. ...Zhuang, Y. / Xu, P. / Mao, C. / Wang, L. / Krumm, B. / Zhou, X.E. / Huang, S. / Liu, H. / Cheng, X. / Huang, X.-P. / Sheng, D.-D. / Xu, T. / Liu, Y.-F. / Wang, Y. / Guo, J. / Jiang, Y. / Jiang, H. / Melcher, K. / Roth, B.L. / Zhang, Y. / Zhang, C. / Xu, H.E. | |||||||||||||||
資金援助 | 中国, 米国, 4件
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引用 | ジャーナル: Cell / 年: 2021 タイトル: Structural insights into the human D1 and D2 dopamine receptor signaling complexes. 著者: Youwen Zhuang / Peiyu Xu / Chunyou Mao / Lei Wang / Brian Krumm / X Edward Zhou / Sijie Huang / Heng Liu / Xi Cheng / Xi-Ping Huang / Dan-Dan Shen / Tinghai Xu / Yong-Feng Liu / Yue Wang / ...著者: Youwen Zhuang / Peiyu Xu / Chunyou Mao / Lei Wang / Brian Krumm / X Edward Zhou / Sijie Huang / Heng Liu / Xi Cheng / Xi-Ping Huang / Dan-Dan Shen / Tinghai Xu / Yong-Feng Liu / Yue Wang / Jia Guo / Yi Jiang / Hualiang Jiang / Karsten Melcher / Bryan L Roth / Yan Zhang / Cheng Zhang / H Eric Xu / 要旨: The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R ...The D1- and D2-dopamine receptors (D1R and D2R), which signal through G and G, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-G and D2R-G signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system. | |||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7jvp.cif.gz | 205.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7jvp.ent.gz | 163.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7jvp.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7jvp_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7jvp_full_validation.pdf.gz | 1.3 MB | 表示 | |
XML形式データ | 7jvp_validation.xml.gz | 34 KB | 表示 | |
CIF形式データ | 7jvp_validation.cif.gz | 51.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/jv/7jvp ftp://data.pdbj.org/pub/pdb/validation_reports/jv/7jvp | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#2: タンパク質 | 分子量: 45624.352 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAS, GNAS1, GSP 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63092 |
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#3: タンパク質 | 分子量: 39077.715 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
#4: タンパク質 | 分子量: 7432.554 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
-タンパク質 / 抗体 , 2種, 2分子 RN
#1: タンパク質 | 分子量: 55668.707 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: DRD1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P21728 |
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#5: 抗体 | 分子量: 14845.516 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / 発現宿主: Escherichia coli (大腸菌) |
-非ポリマー , 3種, 12分子
#6: 化合物 | ChemComp-SK9 / ( | ||
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#7: 化合物 | ChemComp-CLR / #8: 化合物 | ChemComp-PLM / |
-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: SKF-81297-bound dopamine receptor 1 in complex with Gi protein タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.2 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 64 e/Å2 フィルム・検出器のモデル: GATAN K2 BASE (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 679728 / 対称性のタイプ: POINT |