+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7crh | ||||||
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タイトル | Cryo-EM structure of SKF83959 bound dopamine receptor DRD1-Gs signaling complex | ||||||
要素 |
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キーワード | CELL CYCLE / cell signaling | ||||||
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 / sensitization / operant conditioning / Dopamine receptors / modification of postsynaptic structure / regulation of dopamine uptake involved in synaptic transmission / dopamine binding / heterotrimeric G-protein binding ...dopamine neurotransmitter receptor activity, coupled via Gs / dopamine neurotransmitter receptor activity / cerebral cortex GABAergic interneuron migration / sensitization / operant conditioning / Dopamine receptors / modification of postsynaptic structure / regulation of dopamine uptake involved in synaptic transmission / dopamine binding / heterotrimeric G-protein binding / positive regulation of neuron migration / G protein-coupled receptor complex / peristalsis / regulation of dopamine metabolic process / phospholipase C-activating dopamine receptor signaling pathway / grooming behavior / habituation / dopamine transport / astrocyte development / positive regulation of potassium ion transport / conditioned taste aversion / striatum development / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / adult walking behavior / long-term synaptic depression / mating behavior / ciliary membrane / G protein-coupled dopamine receptor signaling pathway / temperature homeostasis / activation of adenylate cyclase activity / dopamine metabolic process / D-glucose import / transmission of nerve impulse / adenylate cyclase-activating adrenergic receptor signaling pathway / behavioral response to cocaine / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / behavioral fear response / neuronal action potential / G-protein alpha-subunit binding / prepulse inhibition / GABA-ergic synapse / synapse assembly / presynaptic modulation of chemical synaptic transmission / response to amphetamine / positive regulation of synaptic transmission, glutamatergic / positive regulation of release of sequestered calcium ion into cytosol / synaptic transmission, glutamatergic / long-term synaptic potentiation / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of protein phosphorylation / visual learning / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / cilium / 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 / G beta:gamma signalling through CDC42 / memory / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / vasodilation / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / protein import into nucleus / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / presynaptic membrane 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Lama glama (ラマ) | ||||||
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: 3.3 Å | ||||||
データ登録者 | Yan, W. / Shao, Z.H. | ||||||
引用 | ジャーナル: Cell / 年: 2021 タイトル: Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes. 著者: Peng Xiao / Wei Yan / Lu Gou / Ya-Ni Zhong / Liangliang Kong / Chao Wu / Xin Wen / Yuan Yuan / Sheng Cao / Changxiu Qu / Xin Yang / Chuan-Cheng Yang / Anjie Xia / Zhenquan Hu / Qianqian Zhang ...著者: Peng Xiao / Wei Yan / Lu Gou / Ya-Ni Zhong / Liangliang Kong / Chao Wu / Xin Wen / Yuan Yuan / Sheng Cao / Changxiu Qu / Xin Yang / Chuan-Cheng Yang / Anjie Xia / Zhenquan Hu / Qianqian Zhang / Yong-Hao He / Dao-Lai Zhang / Chao Zhang / Gui-Hua Hou / Huanxiang Liu / Lizhe Zhu / Ping Fu / Shengyong Yang / Daniel M Rosenbaum / Jin-Peng Sun / Yang Du / Lei Zhang / Xiao Yu / Zhenhua Shao / 要旨: Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five ...Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five cryoelectron microscopy (cryo-EM) structures of the dopamine D1 receptor (DRD1) coupled to Gs heterotrimer in complex with three catechol-based agonists, a non-catechol agonist, and a positive allosteric modulator for endogenous dopamine. These structures revealed that a polar interaction network is essential for catecholamine-like agonist recognition, whereas specific motifs in the extended binding pocket were responsible for discriminating D1- from D2-like receptors. Moreover, allosteric binding at a distinct inner surface pocket improved the activity of DRD1 by stabilizing endogenous dopamine interaction at the orthosteric site. DRD1-Gs interface revealed key features that serve as determinants for G protein coupling. Together, our study provides a structural understanding of the ligand recognition, allosteric regulation, and G protein coupling mechanisms of DRD1. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7crh.cif.gz | 255.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7crh.ent.gz | 197 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7crh.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7crh_validation.pdf.gz | 977.1 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7crh_full_validation.pdf.gz | 992.7 KB | 表示 | |
XML形式データ | 7crh_validation.xml.gz | 34.7 KB | 表示 | |
CIF形式データ | 7crh_validation.cif.gz | 51.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/cr/7crh ftp://data.pdbj.org/pub/pdb/validation_reports/cr/7crh | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#1: タンパク質 | 分子量: 45769.570 Da / 分子数: 1 / 変異: S205T,G226A,A366S / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAS, GNAS1, GSP 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63092 |
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#2: タンパク質 | 分子量: 39141.793 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
#3: 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) Homo sapiens (ヒト) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
-抗体 / タンパク質 / 非ポリマー , 3種, 3分子 NR
#4: 抗体 | 分子量: 16926.076 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Lama glama (ラマ) / 発現宿主: Escherichia coli (大腸菌) |
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#5: タンパク質 | 分子量: 49339.168 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: DRD1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P21728 |
#6: 化合物 | ChemComp-GBU / ( |
-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 |
-試料調製
構成要素 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 | ||||||||||||||||||||||||||||||
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 |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
電子レンズ | モード: OTHER |
撮影 | 電子線照射量: 64 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 140000 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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