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基本情報
登録情報 | データベース: EMDB / ID: EMD-22509 | |||||||||||||||
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タイトル | Cryo-EM structure of SKF-83959-bound dopamine receptor 1 in complex with Gs protein | |||||||||||||||
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![]() | Dopamine receptor 1 / Gi protein / SKF-83959 / SIGNALING PROTEIN | |||||||||||||||
機能・相同性 | ![]() dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / operant conditioning / Dopamine receptors / dopamine binding / regulation of dopamine uptake involved in synaptic transmission / phospholipase C-activating dopamine receptor signaling pathway / peristalsis / heterotrimeric G-protein binding ...dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / operant conditioning / Dopamine receptors / dopamine binding / regulation of dopamine uptake involved in synaptic transmission / phospholipase C-activating dopamine receptor signaling pathway / peristalsis / heterotrimeric G-protein binding / modification of postsynaptic structure / G protein-coupled receptor complex / regulation of dopamine metabolic process / grooming behavior / positive regulation of neuron migration / habituation / sensitization / dopamine transport / astrocyte development / dentate gyrus development / conditioned taste aversion / striatum development / positive regulation of potassium ion transport / maternal behavior / arrestin family protein binding / non-motile cilium / long-term synaptic depression / mating behavior / adult walking behavior / G protein-coupled dopamine receptor signaling pathway / ciliary membrane / temperature homeostasis / D-glucose import / dopamine metabolic process / transmission of nerve impulse / PKA activation in glucagon signalling / developmental growth / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / G-protein alpha-subunit binding / hair follicle placode formation / D1 dopamine receptor binding / positive regulation of synaptic transmission, glutamatergic / behavioral fear response / prepulse inhibition / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / neuronal action potential / renal water homeostasis / activation of adenylate cyclase activity / behavioral response to cocaine / Hedgehog 'off' state / synapse assembly / adenylate cyclase-activating adrenergic receptor signaling pathway / presynaptic modulation of chemical synaptic transmission / cellular response to glucagon stimulus / regulation of insulin secretion / positive regulation of release of sequestered calcium ion into cytosol / response to amphetamine / adenylate cyclase activator activity / trans-Golgi network membrane / synaptic transmission, glutamatergic / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor activity / bone development / visual learning / GABA-ergic synapse / platelet aggregation / G-protein beta/gamma-subunit complex binding / memory / cognition / Olfactory Signaling Pathway / vasodilation / Activation of the phototransduction cascade / long-term synaptic potentiation / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / protein import into nucleus / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma 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: 2.9 Å | |||||||||||||||
![]() | Zhuang Y / Xu P | |||||||||||||||
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. | |||||||||||||||
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 | ![]() | 28.6 MB | ![]() | |
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画像 | ![]() | 69.6 KB | ||
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アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 529.2 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 528.8 KB | 表示 | |
XML形式データ | ![]() | 5.6 KB | 表示 | |
CIF形式データ | ![]() | 6.4 KB | 表示 | |
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EMDBのページ | ![]() ![]() |
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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 | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 : SKF-81297-bound dopamine receptor 1 in complex with Gi protein
全体 | 名称: SKF-81297-bound dopamine receptor 1 in complex with Gi protein |
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要素 |
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-超分子 #1: SKF-81297-bound dopamine receptor 1 in complex with Gi protein
超分子 | 名称: SKF-81297-bound dopamine receptor 1 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: ![]() |
-分子 #1: D(1A) dopamine receptor
分子 | 名称: D(1A) 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: ![]() |
分子量 | 理論値: 55.668707 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASMR TLNTSAMDGT GLVVERDFSV RILTACFLSL LILSTLLGN TLVCAAVIRF RHLRSKVTNF FVISLAVSDL LVAVLVMPWK AVAEIAGFWP FGSFCNIWVA FDIMCSTASI L NLCVISVD ...文字列: DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASMR TLNTSAMDGT GLVVERDFSV RILTACFLSL LILSTLLGN TLVCAAVIRF RHLRSKVTNF FVISLAVSDL LVAVLVMPWK AVAEIAGFWP FGSFCNIWVA FDIMCSTASI L NLCVISVD RYWAISSPFR YERKMTPKAA FILISVAWTL SVLISFIPVQ LSWHKAKPTS PSDGNATSLA ETIDNCDSSL SR TYAISSS VISFYIPVAI MIVTYTRIYR IAQKQIRRIA ALERAAVHAK NCQTTTGNGK PVECSQPESS FKMSFKRETK VLK TLSVIM GVFVCCWLPF FILNCILPFC GSGETQPFCI DSNTFDVFVW FGWANSSLNP IIYAFNADFR KAFSTLLGCY RLCP ATNNA IETVSINNNG AAMFSSHHEP RGSISKECNL VYLIPHAVGS SEDLKKEEAA GIARPLEKLS PALSVILDYD TDVSL EKIQ PITQNGQHPT HHHHHHHH UniProtKB: D(1A) dopamine receptor |
-分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: 45.624352 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GCLGNSKTED QRNEEKAQRE ANKKIEKQLQ KDKQVYRATH RLLLLGAGES GKSTIVKQMR ILHVNGFNGE GGEEDPQAAR SNSDGEKAT KVQDIKNNLK EAIETIVAAM SNLVPPVELA NPENQFRVDY ILSVMNVPDF DFPPEFYEHA KALWEDEGVR A CYERSNEY ...文字列: GCLGNSKTED QRNEEKAQRE ANKKIEKQLQ KDKQVYRATH RLLLLGAGES GKSTIVKQMR ILHVNGFNGE GGEEDPQAAR SNSDGEKAT KVQDIKNNLK EAIETIVAAM SNLVPPVELA NPENQFRVDY ILSVMNVPDF DFPPEFYEHA KALWEDEGVR A CYERSNEY QLIDCAQYFL DKIDVIKQAD YVPSDQDLLR CRVLTSGIFE TKFQVDKVNF HMFDVGAQRD ERRKWIQCFN DV TAIIFVV ASSSYNMVIR EDNQTNRLQE ALNLFKSIWN NRWLRTISVI LFLNKQDLLA EKVLAGKSKI EDYFPEFARY TTP EDATPE PGEDPRVTRA KYFIRDEFLR ISTASGDGRH YCYPHFTCSV DTENIRRVFN DCRDIIQRMH LRQYELL UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-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: ![]() |
分子量 | 理論値: 39.077715 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: HHHHHHHHMG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN ...文字列: HHHHHHHHMG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN QIVTSSGDTT CALWDIETGQ QTTTFTGHTG DVMSLSLAPD TRLFVSGACD ASAKLWDVRE GMCRQTFTGH ES DINAICF FPNGNAFATG SDDATCRLFD LRADQELMTY SHDNIICGIT SVSFSKSGRL LLAGYDDFNC NVWDALKADR AGV LAGHDN RVSCLGVTDD GMAVATGSWD SFLKIWNG 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: ![]() |
分子量 | 理論値: 7.432554 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFC UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: nanobody 35
分子 | 名称: nanobody 35 / 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: 14.845516 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MQVQLQESGG GLVQPGGSLR LSCAASGFTF SNYKMNWVRQ APGKGLEWVS DISQSGASIS YTGSVKGRFT ISRDNAKNTL YLQMNSLKP EDTAVYYCAR CPAPFTRDCF DVTSTTYAYR GQGTQVTVSS HHHHHH |
-分子 #6: (1R)-6-chloro-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3...
分子 | 名称: (1R)-6-chloro-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol タイプ: ligand / ID: 6 / コピー数: 1 / 式: SK9 |
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分子量 | 理論値: 317.81 Da |
Chemical component information | ![]() ChemComp-SK9: |
-分子 #7: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 7 / コピー数: 6 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-分子 #8: PALMITIC ACID
分子 | 名称: PALMITIC ACID / タイプ: ligand / ID: 8 / コピー数: 5 / 式: PLM |
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分子量 | 理論値: 256.424 Da |
Chemical component information | ![]() ChemComp-PLM: |
-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: 7.2 |
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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: ![]() |
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 |