+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8f7x | ||||||||||||
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タイトル | Gi bound nociceptin receptor in complex with nociceptin peptide | ||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN / mu opioid receptor / G protein coupled receptor (Gタンパク質共役受容体) / beta-endorphin | ||||||||||||
機能・相同性 | 機能・相同性情報 nociceptin receptor activity / opioid receptor binding / opioid peptide activity / regulation of locomotor rhythm / conditioned place preference / 知覚 / positive regulation of urine volume / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide hormone activity / neuropeptide binding ...nociceptin receptor activity / opioid receptor binding / opioid peptide activity / regulation of locomotor rhythm / conditioned place preference / 知覚 / positive regulation of urine volume / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide hormone activity / neuropeptide binding / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Ca2+ pathway / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / negative regulation of cAMP-mediated signaling / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / eating behavior / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / photoreceptor outer segment / estrous cycle / neuropeptide signaling pathway / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / cellular response to forskolin / regulation of mitotic spindle organization / cardiac muscle cell apoptotic process / sensory perception of pain / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / negative regulation of blood pressure / photoreceptor inner segment / Peptide ligand-binding receptors / Regulation of insulin secretion / female pregnancy / G protein-coupled receptor activity / G protein-coupled receptor binding / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / response to peptide hormone / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GPER1 signaling / G-protein beta-subunit binding / GDP binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / response to estradiol 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) Rattus norvegicus (ドブネズミ) Bos taurus (ウシ) synthetic construct (人工物) | ||||||||||||
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: 3.28 Å | ||||||||||||
データ登録者 | Wang, Y. / Zhuang, Y. / DiBerto, J.F. / Zhou, X.E. / Schmitz, G.P. / Yuan, Q. / Jain, M.K. / Liu, W. / Melcher, K. / Jiang, Y. ...Wang, Y. / Zhuang, Y. / DiBerto, J.F. / Zhou, X.E. / Schmitz, G.P. / Yuan, Q. / Jain, M.K. / Liu, W. / Melcher, K. / Jiang, Y. / Roth, B.L. / Xu, H.E. | ||||||||||||
資金援助 | 中国, 3件
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引用 | ジャーナル: Cell / 年: 2023 タイトル: Structures of the entire human opioid receptor family. 著者: Yue Wang / Youwen Zhuang / Jeffrey F DiBerto / X Edward Zhou / Gavin P Schmitz / Qingning Yuan / Manish K Jain / Weiyi Liu / Karsten Melcher / Yi Jiang / Bryan L Roth / H Eric Xu / 要旨: Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid ...Opioids are effective analgesics, but their use is beset by serious side effects, including addiction and respiratory depression, which contribute to the ongoing opioid crisis. The human opioid system contains four opioid receptors (μOR, δOR, κOR, and NOPR) and a set of related endogenous opioid peptides (EOPs), which show distinct selectivity toward their respective opioid receptors (ORs). Despite being key to the development of safer analgesics, the mechanisms of molecular recognition and selectivity of EOPs to ORs remain unclear. Here, we systematically characterize the binding of EOPs to ORs and present five structures of EOP-OR-G complexes, including β-endorphin- and endomorphin-bound μOR, deltorphin-bound δOR, dynorphin-bound κOR, and nociceptin-bound NOPR. These structures, supported by biochemical results, uncover the specific recognition and selectivity of opioid peptides and the conserved mechanism of opioid receptor activation. These results provide a structural framework to facilitate rational design of safer opioid drugs for pain relief. | ||||||||||||
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 | 8f7x.cif.gz | 209.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8f7x.ent.gz | 165.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8f7x.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/f7/8f7x ftp://data.pdbj.org/pub/pdb/validation_reports/f7/8f7x | HTTPS FTP |
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-関連構造データ
関連構造データ | 28912MC 8f7qC 8f7rC 8f7sC 8f7wC 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 ABC
#3: タンパク質 | 分子量: 40445.059 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: GNAI1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63096 |
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#4: タンパク質 | 分子量: 39020.664 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Gnb1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P54311 |
#5: タンパク質 | 分子量: 7563.750 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63212 |
-タンパク質 / タンパク質・ペプチド / 抗体 , 3種, 3分子 RPE
#1: タンパク質 | 分子量: 40597.887 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: OPRL1, OOR, ORL1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P41146 |
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#2: タンパク質・ペプチド | 分子量: 1499.760 Da / 分子数: 1 / Fragment: UNP residues 130-143 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: Q13519 |
#6: 抗体 | 分子量: 26408.492 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / 発現宿主: Escherichia coli (大腸菌) |
-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: Gi bound mu-opioid receptor in complex with beta-endorphin タイプ: COMPLEX / Entity ID: all / 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: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.2 |
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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 23.3 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 |
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CTF補正 | タイプ: NONE |
3次元再構成 | 解像度: 3.28 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 184353 / 対称性のタイプ: POINT |