+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-28909 | ||||||||||||
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タイトル | Gi bound delta-opioid receptor in complex with deltorphin | ||||||||||||
マップデータ | |||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 G protein-coupled enkephalin receptor activity / opioid peptide activity / spine apparatus / positive regulation of CREB transcription factor activity / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / cellular response to toxic substance / receptor serine/threonine kinase binding / G-protein activation / Activation of the phototransduction cascade ...G protein-coupled enkephalin receptor activity / opioid peptide activity / spine apparatus / positive regulation of CREB transcription factor activity / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / cellular response to toxic substance / receptor serine/threonine kinase 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 / neuropeptide binding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / 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 / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / 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 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / 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 / neuronal dense core vesicle / regulation of calcium ion transport / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / negative regulation of protein-containing complex assembly / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / dendrite membrane / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / Peptide ligand-binding receptors / adult locomotory behavior / regulation of mitochondrial membrane potential / Regulation of insulin secretion / G protein-coupled receptor binding / postsynaptic density membrane / response to nicotine / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / cellular response to growth factor stimulus / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / defense response / synaptic vesicle membrane / 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 / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Phyllomedusa (カエル) / Rattus norvegicus (ドブネズミ) / Bos taurus (ウシ) | ||||||||||||
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 | Wang Y / Zhuang Y / DiBerto JF / Zhou XE / Schmitz GP / Yuan Q / Jain MK / Liu W / Melcher K / Jiang Y ...Wang Y / Zhuang Y / DiBerto JF / Zhou XE / Schmitz GP / Yuan Q / Jain MK / Liu W / Melcher K / Jiang Y / Roth BL / Xu HE | ||||||||||||
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
添付画像 |
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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_28909.map.gz | 59.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-28909-v30.xml emd-28909.xml | 20.2 KB 20.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_28909.png | 135 KB | ||
その他 | emd_28909_half_map_1.map.gz emd_28909_half_map_2.map.gz | 49.5 MB 49.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-28909 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28909 | 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_28909.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.84 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #1
ファイル | emd_28909_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_28909_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Gi bound mu-opioid receptor in complex with beta-endorphin
全体 | 名称: Gi bound mu-opioid receptor in complex with beta-endorphin |
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要素 |
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-超分子 #1: Gi bound mu-opioid receptor in complex with beta-endorphin
超分子 | 名称: Gi bound mu-opioid receptor in complex with beta-endorphin タイプ: complex / ID: 1 / キメラ: Yes / 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: Delta-type opioid receptor
分子 | 名称: Delta-type opioid receptor / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 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: 42.65102 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: DYKDDDDVDA SEPAPSAGAE LQPPLFANAS DAYPSACPSA GANASGPPGA RSASSLALAI AITALYSAVC AVGLLGNVLV MFVIVRYTK MKTATNIYIF SLALAGALAT STLPFQSAKY LMETWPFGEL LCKAVLSIDY YSMFTSIFTL TMMCVDRYIA V CHPVKALD ...文字列: DYKDDDDVDA SEPAPSAGAE LQPPLFANAS DAYPSACPSA GANASGPPGA RSASSLALAI AITALYSAVC AVGLLGNVLV MFVIVRYTK MKTATNIYIF SLALAGALAT STLPFQSAKY LMETWPFGEL LCKAVLSIDY YSMFTSIFTL TMMCVDRYIA V CHPVKALD FRTPAKAKLI NICIWVLASG VGVPIMVMAV TRPRDGAVVC MLQFPSPSWY WDTVTKICVF LFAFVVPILI IT VCYGLML LRLRSVRLLS GSKEKDRSLR RITRMVLVVV VAFVVCWAPI HIFVIVWTLV DIDRRDPLVV AALHLCIALG YIN SSLNPV LYAFLDENFK RCFRQLCRKP CGRPDPSSFS RAREATARER VTACTPSDGP GGGAAAHHHH HHHH |
-分子 #2: deltorphin
分子 | 名称: deltorphin / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Phyllomedusa (カエル) |
分子量 | 理論値: 781.876 Da |
配列 | 文字列: Y(DAL)FEVVG(NH2) |
-分子 #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 3 / コピー数: 2 / 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: 40.445059 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-分子 #4: 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: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 39.020664 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MHHHHHHHHG SLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQD GKLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL S CCRFLDDN ...文字列: MHHHHHHHHG 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 SFLKIWN |
-分子 #5: 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: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Bos taurus (ウシ) |
分子量 | 理論値: 7.56375 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFC |
-分子 #6: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 6 / 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 #7: PALMITIC ACID
分子 | 名称: PALMITIC ACID / タイプ: ligand / ID: 7 / コピー数: 12 / 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 |
-試料調製
緩衝液 | pH: 7.2 |
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凍結 | 凍結剤: ETHANE |
-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 K3 (6k x 4k) / 平均電子線量: 23.3 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 / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 0.8 µm |
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: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 650970 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |