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基本情報
登録情報 | データベース: EMDB / ID: EMD-21243 | |||||||||
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タイトル | Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane | |||||||||
![]() | Catecholamine receptor structure | |||||||||
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![]() | Dopamine / Dopamine receptor / GPCR / G protein / Parkinson's disease / SIGNALING PROTEIN | |||||||||
機能・相同性 | ![]() negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / 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 / regulation of synapse structural plasticity / response to histamine ...negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / 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 / regulation of synapse structural plasticity / response to histamine / regulation of locomotion involved in locomotory behavior / neuron-neuron synaptic transmission / adenohypophysis development / positive regulation of renal sodium excretion / Extra-nuclear estrogen signaling / negative regulation of cellular response to hypoxia / positive regulation of growth hormone secretion / regulation of potassium ion transport / hyaloid vascular plexus regression / cerebral cortex GABAergic interneuron migration / Adenylate cyclase inhibitory pathway / negative regulation of dopamine secretion / adenylate cyclase-inhibiting dopamine receptor signaling pathway / response to inactivity / Dopamine receptors / orbitofrontal cortex development / negative regulation of neuron migration / regulation of dopamine uptake involved in synaptic transmission / branching morphogenesis of a nerve / dopamine binding / phospholipase C-activating dopamine receptor signaling pathway / heterotrimeric G-protein binding / peristalsis / drinking behavior / G protein-coupled receptor complex / grooming behavior / behavioral response to ethanol / auditory behavior / positive regulation of G protein-coupled receptor signaling pathway / dopaminergic synapse / striatum development / negative regulation of adenylate cyclase activity / positive regulation of urine volume / positive regulation of multicellular organism growth / negative regulation of synaptic transmission / G protein-coupled receptor internalization / negative regulation of synaptic transmission, glutamatergic / GTPase activating protein binding / cellular response to ethanol / non-motile cilium / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / response to iron ion / G alpha (i) signalling events / adult walking behavior / response to morphine / ciliary membrane / neurotransmitter receptor localization to postsynaptic specialization membrane / arachidonate secretion / negative regulation of cytosolic calcium ion concentration / pigmentation / temperature homeostasis / heterocyclic compound binding / positive regulation of neuroblast proliferation / regulation of synaptic transmission, GABAergic / dopamine uptake involved in synaptic transmission / regulation of dopamine secretion / positive regulation of cytokinesis / dopamine metabolic process / associative learning / behavioral response to cocaine / positive regulation of receptor internalization / sperm flagellum / response to light stimulus / endocytic vesicle / neuroblast proliferation / G-protein alpha-subunit binding / long-term memory / response to axon injury / negative regulation of protein secretion / lateral plasma membrane / postsynaptic modulation of chemical synaptic transmission / prepulse inhibition / potassium channel regulator activity / negative regulation of insulin secretion / viral release from host cell by cytolysis / positive regulation of protein localization to cell cortex / T cell migration / synapse assembly / regulation of sodium ion transport / D2 dopamine receptor binding / cellular response to retinoic acid / ionotropic glutamate 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 / axon terminus / release of sequestered calcium ion into cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | |||||||||
![]() | Yin J / Chen KM | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane. 著者: Jie Yin / Kuang-Yui M Chen / Mary J Clark / Mahdi Hijazi / Punita Kumari / Xiao-Chen Bai / Roger K Sunahara / Patrick Barth / Daniel M Rosenbaum / ![]() ![]() 要旨: The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such ...The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine, leading to stimulation of G and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-G complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular G-binding site. The DRD2-G structure represents, to our knowledge, the first experimental model of a G-protein-coupled receptor-G-protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine side chains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help to inform the design of subtype-selective DRD2 ligands for multiple human central nervous system disorders. | |||||||||
履歴 |
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 78.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.7 KB 16.7 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 10.1 KB | 表示 | ![]() |
画像 | ![]() | 18.8 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Catecholamine receptor structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 0.83 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 : D2 dopamine receptor-G protein complex
全体 | 名称: D2 dopamine receptor-G protein complex |
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要素 |
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-超分子 #1: D2 dopamine receptor-G protein complex
超分子 | 名称: D2 dopamine receptor-G protein complex / 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: ![]() |
-分子 #1: 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: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 40.382047 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDAA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDAA 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 THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #2: 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: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 37.41693 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: 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: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 9.137474 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGHHHHHHHH GGASNNTASI AQARKLVEQL KMEANIDRIK VSKAAADLMA YCEAHAKEDP LLTPVPASEN PFREKKFFCA IL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: scFv16
分子 | 名称: scFv16 / 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: ![]() |
分子量 | 理論値: 27.784896 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 KAAAHHHHHH HH |
-分子 #5: Endolysin,D(2) dopamine receptor,D(2) dopamine receptor
分子 | 名称: Endolysin,D(2) dopamine receptor,D(2) dopamine receptor タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO / EC番号: lysozyme |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 51.384059 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DYKDDDDANI FEMLRIDEGL RLKIYKNTEG YYTIGIGHLL TKSPSLNAAK SELDKAIGRN TNGVITKDEA EKLFNQDVDA AVRGILRNA KLKPVYDSLD AVRRAALINM VFQMGETGVA GFTNSLRMLQ QKRWDEAAVN LAKSRWYNQT PNRAKRVITT F RTGTWDAY ...文字列: DYKDDDDANI FEMLRIDEGL RLKIYKNTEG YYTIGIGHLL TKSPSLNAAK SELDKAIGRN TNGVITKDEA EKLFNQDVDA AVRGILRNA KLKPVYDSLD AVRRAALINM VFQMGETGVA GFTNSLRMLQ QKRWDEAAVN LAKSRWYNQT PNRAKRVITT F RTGTWDAY AADRPHYNYY ATLLTLLIAV IVFGNVLVCM AVSREKALQT TTNYLIVSLA VADLLVATLV MPWVVYLEVV GE WKFSRIH CDIFVTLDVM MCTASILNLC AISIDRYTAV AMPMLYNTRY SSKRRVTVMI SIVWVLSFTI SCPLLFGLNN ADQ NECIIA NPAFVVYSSI VSFYVPFIVI LLVYIKIYIV LRRRRKLVNT NRKLSQQKEK KATQLLAIYL GLFIICWLPF FITH ILNIH CDCNIPPVLY SAFTWLGYVN SAINPIIYTT FNIEFRKAFL KILHC UniProtKB: Endolysin, D(2) dopamine receptor, D(2) dopamine receptor |
-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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![]() | 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: 7.4 |
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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 K3 BIOQUANTUM (6k 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: ![]() |
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 |