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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-22510 | |||||||||||||||
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| タイトル | Cryo-EM structure of apomorphine-bound dopamine receptor 1 in complex with Gs protein | |||||||||||||||
マップデータ | ||||||||||||||||
試料 |
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キーワード | Dopamine receptor 1 / Gi protein / apomorphine / SIGNALING PROTEIN | |||||||||||||||
| 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 / Dopamine receptors / regulation of dopamine uptake involved in synaptic transmission / dopamine binding / operant conditioning / phospholipase C-activating dopamine receptor signaling pathway / heterotrimeric G-protein binding / peristalsis ...dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / Dopamine receptors / regulation of dopamine uptake involved in synaptic transmission / dopamine binding / operant conditioning / phospholipase C-activating dopamine receptor signaling pathway / heterotrimeric G-protein binding / peristalsis / G protein-coupled receptor complex / modification of postsynaptic structure / positive regulation of neuron migration / habituation / grooming behavior / regulation of dopamine metabolic process / astrocyte development / sensitization / striatum development / dopamine transport / dentate gyrus development / positive regulation of potassium ion transport / conditioned taste aversion / maternal behavior / arrestin family protein binding / non-motile cilium / long-term synaptic depression / G protein-coupled dopamine receptor signaling pathway / mating behavior / adult walking behavior / : / ciliary membrane / temperature homeostasis / dopamine metabolic process / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / transmission of nerve impulse / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / G-protein alpha-subunit binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / behavioral fear response / activation of adenylate cyclase activity / Hedgehog 'off' state / neuronal action potential / positive regulation of synaptic transmission, glutamatergic / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to acidic pH / behavioral response to cocaine / synapse assembly / cellular response to glucagon stimulus / intracellular glucose homeostasis / presynaptic modulation of chemical synaptic transmission / adenylate cyclase activator activity / positive regulation of insulin secretion involved in cellular response to glucose stimulus / positive regulation of release of sequestered calcium ion into cytosol / trans-Golgi network membrane / response to amphetamine / negative regulation of inflammatory response to antigenic stimulus / synaptic transmission, glutamatergic / response to prostaglandin E / bone development / visual learning / platelet aggregation / G protein-coupled receptor activity / vasodilation / GABA-ergic synapse / cognition / G-protein beta/gamma-subunit complex binding / memory / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / protein import into nucleus / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / positive regulation of insulin secretion / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / sensory perception of smell / 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 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: 3.0 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. | |||||||||||||||
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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 |
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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_22510.map.gz | 17.9 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-22510-v30.xml emd-22510.xml | 19.6 KB 19.6 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_22510.png | 62.7 KB | ||
| Filedesc metadata | emd-22510.cif.gz | 7 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22510 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22510 | 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_22510.map.gz / 形式: CCP4 / 大きさ: 27 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: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: Homo sapiens (ヒト) |
-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: Homo sapiens (ヒト) |
| 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: Engineered mini-Gi protein alpha sub-unit
| 分子 | 名称: Engineered mini-Gi protein alpha sub-unit / 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: 29.048932 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHVNSGIF ETKFQVDKVN FHMFDVGAQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...文字列: MGCLGNSKTE DQRNEEKAQR EANKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHVNSGIF ETKFQVDKVN FHMFDVGAQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCS VDTENARRIF NDCRDIIQRM HL RQYELL |
-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: 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: Homo sapiens (ヒト) |
| 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: Nanobody35
| 分子 | 名称: Nanobody35 / 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: (6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,1...
| 分子 | 名称: (6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol タイプ: ligand / ID: 6 / コピー数: 1 / 式: OR9 |
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| 分子量 | 理論値: 267.322 Da |
| Chemical component information | ![]() ChemComp-OR9: |
-分子 #7: CHOLESTEROL
| 分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 7 / コピー数: 5 / 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: 3 / 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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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






































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解析

