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データを開く
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基本情報
| 登録情報 | データベース: EMDB / ID: EMD-22511 | |||||||||||||||
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| タイトル | Cryo-EM structure of Bromocriptine-bound dopamine receptor 2 in complex with Gi protein | |||||||||||||||
マップデータ | ||||||||||||||||
試料 |
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キーワード | Dopamine receptor 2 / Gi protein / bromocriptine / SIGNALING PROTEIN | |||||||||||||||
| 機能・相同性 | 機能・相同性情報negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / response to histamine / negative regulation of circadian sleep/wake cycle, sleep / regulation of synapse structural plasticity ...negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / response to histamine / negative regulation of circadian sleep/wake cycle, sleep / regulation of synapse structural plasticity / regulation of locomotion involved in locomotory behavior / neuron-neuron synaptic transmission / adenohypophysis development / negative regulation of dopamine secretion / positive regulation of renal sodium excretion / negative regulation of cellular response to hypoxia / hyaloid vascular plexus regression / adenylate cyclase-inhibiting dopamine receptor signaling pathway / orbitofrontal cortex development / cerebral cortex GABAergic interneuron migration / response to inactivity / regulation of potassium ion transport / Dopamine receptors / negative regulation of neuron migration / dopamine binding / branching morphogenesis of a nerve / regulation of dopamine uptake involved in synaptic transmission / phospholipase C-activating dopamine receptor signaling pathway / positive regulation of growth hormone secretion / peristalsis / heterotrimeric G-protein binding / drinking behavior / G protein-coupled receptor complex / grooming behavior / behavioral response to ethanol / auditory behavior / positive regulation of G protein-coupled receptor signaling pathway / striatum development / dopaminergic synapse / positive regulation of urine volume / positive regulation of multicellular organism growth / G protein-coupled receptor internalization / non-motile cilium / heterocyclic compound binding / negative regulation of synaptic transmission, glutamatergic / response to iron ion / adult walking behavior / arachidonate secretion / response to morphine / ciliary membrane / negative regulation of cytosolic calcium ion concentration / temperature homeostasis / positive regulation of neuroblast proliferation / regulation of synaptic transmission, GABAergic / positive regulation of cytokinesis / pigmentation / dopamine metabolic process / dopamine uptake involved in synaptic transmission / regulation of dopamine secretion / cellular response to ethanol / associative learning / response to light stimulus / positive regulation of receptor internalization / lateral plasma membrane / neuroblast proliferation / endocytic vesicle / G-protein alpha-subunit binding / negative regulation of protein secretion / long-term memory / potassium channel regulator activity / sperm flagellum / prepulse inhibition / response to axon injury / postsynaptic modulation of chemical synaptic transmission / adenylate cyclase inhibitor activity / synapse assembly / positive regulation of protein localization to cell cortex / negative regulation of blood pressure / T cell migration / regulation of sodium ion transport / behavioral response to cocaine / Adenylate cyclase inhibitory pathway / cellular response to retinoic acid / D2 dopamine receptor binding / response to prostaglandin E / release of sequestered calcium ion into cytosol / axon terminus / ionotropic glutamate receptor binding / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / presynaptic modulation of chemical synaptic transmission / acrosomal vesicle / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to forskolin / axonogenesis / regulation of heart rate / negative regulation of innate immune response / negative regulation of cell migration / regulation of mitotic spindle organization 類似検索 - 分子機能 | |||||||||||||||
| 生物種 | Homo sapiens (ヒト) / 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: 2.8 Å | |||||||||||||||
データ登録者 | Zhuang Y / Xu P | |||||||||||||||
| 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 | EMマップ: SurfView Molmil Jmol/JSmol |
| 添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_22511.map.gz | 26.4 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-22511-v30.xml emd-22511.xml | 20.8 KB 20.8 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_22511.png | 63.8 KB | ||
| Filedesc metadata | emd-22511.cif.gz | 7.3 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22511 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22511 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_22511_validation.pdf.gz | 394.2 KB | 表示 | EMDB検証レポート |
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| 文書・詳細版 | emd_22511_full_validation.pdf.gz | 393.8 KB | 表示 | |
| XML形式データ | emd_22511_validation.xml.gz | 5.6 KB | 表示 | |
| CIF形式データ | emd_22511_validation.cif.gz | 6.4 KB | 表示 | |
| アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22511 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22511 | HTTPS FTP |
-関連構造データ
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リンク
| EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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| 「今月の分子」の関連する項目 |
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マップ
| ファイル | ダウンロード / ファイル: emd_22511.map.gz / 形式: CCP4 / 大きさ: 30.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ボクセルのサイズ | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 密度 |
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : Bromocriptin-bound dopamine receptor 2 in complex with Gi protein
| 全体 | 名称: Bromocriptin-bound dopamine receptor 2 in complex with Gi protein |
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| 要素 |
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-超分子 #1: Bromocriptin-bound dopamine receptor 2 in complex with Gi protein
| 超分子 | 名称: Bromocriptin-bound dopamine receptor 2 in complex with Gi protein タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Soluble cytochrome b562,D(2) dopamine receptor
| 分子 | 名称: Soluble cytochrome b562,D(2) dopamine receptor / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 67.234578 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: DYKDDDDAKL QTMHHHHHHH HHHHHHHHAD LEDNWETLND NLKVIEKADN AAQVKDALTK MRAAALDAQK ATPPKLEDKS PDSPEMKDF RHGFDILVGQ IDDALKLANE GKVKEAQAAA EQLKTTRNAY IQKYLASENL YFQGGTMDPL NLSWYDDDLE R QNWSRPFN ...文字列: DYKDDDDAKL QTMHHHHHHH HHHHHHHHAD LEDNWETLND NLKVIEKADN AAQVKDALTK MRAAALDAQK ATPPKLEDKS PDSPEMKDF RHGFDILVGQ IDDALKLANE GKVKEAQAAA EQLKTTRNAY IQKYLASENL YFQGGTMDPL NLSWYDDDLE R QNWSRPFN GSDGKADRPH YNYYATLLTL LIAVIVFGNV LVCMAVSREK ALQTTTNYLI VSLAVADLLV ATLVMPWVVY LE VVGEWKF SRIHCDIFVT LDVMMCTASI LNLCAISIDR YTAVAMPMLY NTRYSSKRRV TVMISIVWVL SFTISCPLLF GLN NADQNE CIIANPAFVV YSSIVSFYVP FIVTLLVYIK IYIVLRRRRK RVNTKRSSRA FRAHLRAPLK GNCTHPEDMK LCTV IMKSN GSFPVNRRRV EAARRAQELE MEMLSSTSPP ERTRYSPIPP SHHQLTLPDP SHHGLHSTPD SPAKPEKNGH AKDHP KIAK IFEIQTMPNG KTRTSLKTMS RRKLSQQKEK KATQMLAIVL GVFIICWLPF FITHILNIHC DCNIPPVLYS AFTWLG YVN SAVNPIIYTT FNIEFRKAFL KILHC UniProtKB: Soluble cytochrome b562, D(2) dopamine receptor |
-分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
| 分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 40.414047 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 38.146707 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...文字列: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWNG SS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 7.861143 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: Antibody fragment ScFv16
| 分子 | 名称: Antibody fragment ScFv16 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: synthetic construct (人工物) |
| 分子量 | 理論値: 28.813047 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KGSLEVLFQG PAAAHHHHHH HH |
-分子 #6: bromoergocryptine
| 分子 | 名称: bromoergocryptine / タイプ: ligand / ID: 6 / コピー数: 1 / 式: 08Y |
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| 分子量 | 理論値: 654.594 Da |
| Chemical component information | ![]() ChemComp-08Y: |
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
| 試料の集合状態 | particle |
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試料調製
| 緩衝液 | pH: 7.2 |
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| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | FEI TITAN KRIOS |
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| 撮影 | フィルム・検出器のモデル: GATAN K2 BASE (4k x 4k) 平均電子線量: 64.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
ムービー
コントローラー
万見について



キーワード
Homo sapiens (ヒト)
データ登録者
中国,
米国, 4件
引用
UCSF Chimera















































Z (Sec.)
Y (Row.)
X (Col.)
























解析

