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基本情報
登録情報 | データベース: PDB / ID: 7jvr | |||||||||||||||
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タイトル | Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in complex with Gi protein | |||||||||||||||
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![]() | SIGNALING PROTEIN / Dopamine receptor 2 / Gi protein / bromocriptine | |||||||||||||||
機能・相同性 | ![]() regulation of locomotion involved in locomotory behavior / negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of circadian sleep/wake cycle, sleep / acid secretion / positive regulation of glial cell-derived neurotrophic factor production / dopamine neurotransmitter receptor activity, coupled via Gi/Go / auditory behavior / nervous system process involved in regulation of systemic arterial blood pressure / regulation of synapse structural plasticity ...regulation of locomotion involved in locomotory behavior / negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of circadian sleep/wake cycle, sleep / acid secretion / positive regulation of glial cell-derived neurotrophic factor production / dopamine neurotransmitter receptor activity, coupled via Gi/Go / auditory behavior / nervous system process involved in regulation of systemic arterial blood pressure / regulation of synapse structural plasticity / response to histamine / positive regulation of renal sodium excretion / adenohypophysis development / neuron-neuron synaptic transmission / hyaloid vascular plexus regression / cerebral cortex GABAergic interneuron migration / regulation of potassium ion transport / negative regulation of neuron migration / Dopamine receptors / adenylate cyclase-inhibiting dopamine receptor signaling pathway / negative regulation of cellular response to hypoxia / orbitofrontal cortex development / response to inactivity / dopamine binding / regulation of dopamine uptake involved in synaptic transmission / branching morphogenesis of a nerve / negative regulation of voltage-gated calcium channel activity / negative regulation of dopamine secretion / positive regulation of growth hormone secretion / heterotrimeric G-protein binding / behavioral response to ethanol / dopaminergic synapse / drinking behavior / peristalsis / G protein-coupled receptor complex / phospholipase C-activating dopamine receptor signaling pathway / grooming behavior / positive regulation of G protein-coupled receptor signaling pathway / positive regulation of urine volume / striatum development / negative regulation of adenylate cyclase activity / positive regulation of multicellular organism growth / negative regulation of synaptic transmission, glutamatergic / G protein-coupled receptor internalization / non-motile cilium / response to morphine / adult walking behavior / response to iron ion / ciliary membrane / dopamine uptake involved in synaptic transmission / regulation of synaptic transmission, GABAergic / arachidonic acid secretion / temperature homeostasis / pigmentation / postsynaptic modulation of chemical synaptic transmission / heterocyclic compound binding / dopamine metabolic process / positive regulation of neuroblast proliferation / negative regulation of cytosolic calcium ion concentration / regulation of dopamine secretion / positive regulation of cytokinesis / associative learning / positive regulation of receptor internalization / behavioral response to cocaine / lateral plasma membrane / endocytic vesicle / G-protein alpha-subunit binding / neuroblast proliferation / response to axon injury / response to light stimulus / GABA-ergic synapse / potassium channel regulator activity / sperm flagellum / negative regulation of protein secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / prepulse inhibition / long-term memory / G protein-coupled serotonin receptor binding / axon terminus / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of sodium ion transport / release of sequestered calcium ion into cytosol / regulation of mitotic spindle organization / cellular response to forskolin / synapse assembly / response to amphetamine / presynaptic modulation of chemical synaptic transmission / negative regulation of blood pressure / negative regulation of innate immune response / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / excitatory postsynaptic potential / regulation of heart rate / negative regulation of cell migration / axonogenesis / phosphatidylinositol 3-kinase/protein kinase B signal transduction 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() ![]() ![]() 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: 2.8 Å | |||||||||||||||
![]() | 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 | ![]() ![]()
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![]() | ![]() 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. | |||||||||||||||
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 238.9 KB | 表示 | ![]() |
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PDB形式 | ![]() | 187.6 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 812.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 820 KB | 表示 | |
XML形式データ | ![]() | 34 KB | 表示 | |
CIF形式データ | ![]() | 52.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABC
#2: タンパク質 | 分子量: 40414.047 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P63096 |
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#3: タンパク質 | 分子量: 38146.707 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P62873 |
#4: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P59768 |
-タンパク質 / 抗体 / 非ポリマー , 3種, 3分子 RE![](data/chem/img/08Y.gif)
![](data/chem/img/08Y.gif)
#1: タンパク質 | 分子量: 67234.578 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() 遺伝子: cybC, DRD2 発現宿主: ![]() ![]() 参照: UniProt: P0ABE7, UniProt: P14416 |
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#5: 抗体 | 分子量: 28813.047 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: ![]() ![]() |
#6: 化合物 | ChemComp-08Y / |
-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 |
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試料調製
構成要素 | 名称: Bromocriptin-bound dopamine receptor 2 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: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
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 |
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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: ![]() |
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) |
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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: NONE |
3次元再構成 | 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 632558 / 対称性のタイプ: POINT |