+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30394 | |||||||||
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タイトル | Cryo-EM structure of PW0464 bound dopamine receptor DRD1-Gs signaling complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | signaling complex / CELL CYCLE | |||||||||
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 / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / 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 / regulation of dopamine uptake involved in synaptic transmission / modification of postsynaptic structure / dopamine binding / heterotrimeric G-protein binding / G protein-coupled receptor complex / peristalsis / regulation of dopamine metabolic process / grooming behavior / phospholipase C-activating dopamine receptor signaling pathway / positive regulation of neuron migration / habituation / dopamine transport / positive regulation of potassium ion transport / astrocyte development / conditioned taste aversion / striatum development / dentate gyrus development / maternal behavior / arrestin family protein binding / non-motile cilium / long-term synaptic depression / mating behavior / adult walking behavior / ciliary membrane / G protein-coupled dopamine receptor signaling pathway / temperature homeostasis / D-glucose import / transmission of nerve impulse / dopamine metabolic process / PKA activation in glucagon signalling / behavioral response to cocaine / hair follicle placode formation / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / behavioral fear response / developmental growth / neuronal action potential / G-protein alpha-subunit binding / D1 dopamine receptor binding / intracellular transport / renal water homeostasis / Hedgehog 'off' state / prepulse inhibition / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / GABA-ergic synapse / cellular response to glucagon stimulus / synapse assembly / adenylate cyclase activator activity / presynaptic modulation of chemical synaptic transmission / response to amphetamine / regulation of insulin secretion / positive regulation of synaptic transmission, glutamatergic / positive regulation of release of sequestered calcium ion into cytosol / trans-Golgi network membrane / synaptic transmission, glutamatergic / long-term synaptic potentiation / G protein-coupled receptor activity / negative regulation of inflammatory response to antigenic stimulus / bone development / regulation of protein phosphorylation / visual learning / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / cilium / G protein-coupled acetylcholine receptor signaling pathway / G protein activity / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / memory / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / vasodilation / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / protein import into nucleus 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.2 Å | |||||||||
データ登録者 | Yan W / Shao Z | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_30394.map.gz | 36 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30394-v30.xml emd-30394.xml | 17.5 KB 17.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30394.png | 51.6 KB | ||
Filedesc metadata | emd-30394.cif.gz | 6.3 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30394 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30394 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30394_validation.pdf.gz | 532.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30394_full_validation.pdf.gz | 531.8 KB | 表示 | |
XML形式データ | emd_30394_validation.xml.gz | 5 KB | 表示 | |
CIF形式データ | emd_30394_validation.cif.gz | 5.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30394 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30394 | HTTPS FTP |
-関連構造データ
-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 |
-マップ
ファイル | ダウンロード / ファイル: emd_30394.map.gz / 形式: CCP4 / 大きさ: 38.4 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 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
-試料の構成要素
+全体 : Complex structure-3
+超分子 #1: Complex structure-3
+超分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha, beta, gamma
+超分子 #3: Nanobody 35
+超分子 #4: D(1A) dopamine receptor
+分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #2: 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 #4: Nanobody 35
+分子 #5: D(1A) dopamine receptor
+分子 #6: CHOLESTEROL
+分子 #7: 6-[4-[3-[bis(fluoranyl)methoxy]pyridin-2-yl]oxy-2-methyl-phenyl]-...
-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 |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277.15 K |
-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 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 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: OTHER / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 672934 |
初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |