+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8irv | ||||||
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タイトル | Dopamine Receptor D5R-Gs-Rotigotine complex | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN / Dopamine / Dopamine receptor / GPCR / D5R / Gs / Rotigotine / Parkinson's disease / Restless legs syndrome | ||||||
機能・相同性 | 機能・相同性情報 regulation of female receptivity / norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure / regulation of systemic arterial blood pressure by vasopressin / dopamine neurotransmitter receptor activity / Dopamine receptors / dopamine neurotransmitter receptor activity, coupled via Gs / dopamine binding / sensitization / positive regulation of adenylate cyclase activity / phospholipase C-activating dopamine receptor signaling pathway ...regulation of female receptivity / norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure / regulation of systemic arterial blood pressure by vasopressin / dopamine neurotransmitter receptor activity / Dopamine receptors / dopamine neurotransmitter receptor activity, coupled via Gs / dopamine binding / sensitization / positive regulation of adenylate cyclase activity / phospholipase C-activating dopamine receptor signaling pathway / synaptic transmission, dopaminergic / non-motile cilium / long-term synaptic depression / ciliary membrane / G protein-coupled dopamine receptor signaling pathway / negative regulation of NAD(P)H oxidase activity / transmission of nerve impulse / associative learning / adenylate cyclase-activating adrenergic receptor signaling pathway / response to amphetamine / activation of adenylate cyclase activity / negative regulation of blood pressure / reactive oxygen species metabolic process / response to cocaine / G protein-coupled receptor activity / electron transport chain / brush border membrane / wound healing / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / cilium / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / intracellular calcium ion homeostasis / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / iron ion binding / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / heme binding / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Escherichia coli (大腸菌) | ||||||
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: 3.1 Å | ||||||
データ登録者 | Xu, P. / Huang, S. / Zhuang, Y. / Mao, C. / Zhang, Y. / Wang, Y. / Li, H. / Jiang, Y. / Zhang, Y. / Xu, H.E. | ||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Res / 年: 2023 タイトル: Structural genomics of the human dopamine receptor system. 著者: Peiyu Xu / Sijie Huang / Brian E Krumm / Youwen Zhuang / Chunyou Mao / Yumu Zhang / Yue Wang / Xi-Ping Huang / Yong-Feng Liu / Xinheng He / Huadong Li / Wanchao Yin / Yi Jiang / Yan Zhang / ...著者: Peiyu Xu / Sijie Huang / Brian E Krumm / Youwen Zhuang / Chunyou Mao / Yumu Zhang / Yue Wang / Xi-Ping Huang / Yong-Feng Liu / Xinheng He / Huadong Li / Wanchao Yin / Yi Jiang / Yan Zhang / Bryan L Roth / H Eric Xu / 要旨: The dopaminergic system, including five dopamine receptors (D1R to D5R), plays essential roles in the central nervous system (CNS); and ligands that activate dopamine receptors have been used to ...The dopaminergic system, including five dopamine receptors (D1R to D5R), plays essential roles in the central nervous system (CNS); and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders, including Parkinson's Disease (PD) and schizophrenia. Here, we report cryo-EM structures of all five subtypes of human dopamine receptors in complex with G protein and bound to the pan-agonist, rotigotine, which is used to treat PD and restless legs syndrome. The structures reveal the basis of rotigotine recognition in different dopamine receptors. Structural analysis together with functional assays illuminate determinants of ligand polypharmacology and selectivity. The structures also uncover the mechanisms of dopamine receptor activation, unique structural features among the five receptor subtypes, and the basis of G protein coupling specificity. Our work provides a comprehensive set of structural templates for the rational design of specific ligands to treat CNS diseases targeting the dopaminergic system. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8irv.cif.gz | 338.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8irv.ent.gz | 273 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8irv.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 | 8irv_validation.pdf.gz | 1.6 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8irv_full_validation.pdf.gz | 1.6 MB | 表示 | |
XML形式データ | 8irv_validation.xml.gz | 33.5 KB | 表示 | |
CIF形式データ | 8irv_validation.cif.gz | 50.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ir/8irv ftp://data.pdbj.org/pub/pdb/validation_reports/ir/8irv | HTTPS FTP |
-関連構造データ
関連構造データ | 35687MC 8irrC 8irsC 8irtC 8iruC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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: 41748.270 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Trichoplusia ni (イラクサキンウワバ) |
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#2: タンパク質 | 分子量: 38146.707 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: Trichoplusia ni (イラクサキンウワバ) / 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: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P59768 |
-タンパク質 , 1種, 1分子 R
#4: タンパク質 | 分子量: 68847.297 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Escherichia coli (大腸菌), (組換発現) Homo sapiens (ヒト) 遺伝子: cybC, DRD5, DRD1B, DRD1L2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P0ABE7, UniProt: P21918 |
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-非ポリマー , 3種, 12分子
#5: 化合物 | ChemComp-R5F / | ||
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#6: 化合物 | ChemComp-CLR / #7: 化合物 | ChemComp-PLM / | |
-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 | 名称: Dopamine Receptor D5R-Gs-Rotigotine complex / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) |
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-PROPANE |
-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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2200 nm / 最小 デフォーカス(公称値): 1200 nm / Cs: 2.7 mm |
撮影 | 電子線照射量: 64 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 4746 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 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: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 2652297 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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