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基本情報
登録情報 | ![]() | ||||||||||||
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タイトル | Gi bound mu-opioid receptor in complex with beta-endorphin | ||||||||||||
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![]() | mu opioid receptor / G protein coupled receptor / beta-endorphin / SIGNALING PROTEIN | ||||||||||||
機能・相同性 | ![]() cellular pigmentation / positive regulation of oxytocin production / Peptide hormone biosynthesis / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / regulation of corticosterone secretion / response to melanocyte-stimulating hormone / positive regulation of cAMP-mediated signaling ...cellular pigmentation / positive regulation of oxytocin production / Peptide hormone biosynthesis / Defective ACTH causes obesity and POMCD / type 1 melanocortin receptor binding / type 3 melanocortin receptor binding / type 4 melanocortin receptor binding / regulation of corticosterone secretion / response to melanocyte-stimulating hormone / positive regulation of cAMP-mediated signaling / Opioid Signalling / Androgen biosynthesis / regulation of appetite / beta-endorphin receptor activity / morphine receptor activity / negative regulation of Wnt protein secretion / regulation of glycogen metabolic process / Glucocorticoid biosynthesis / negative regulation of cAMP-mediated signaling / regulation of cellular response to stress / G protein-coupled opioid receptor signaling pathway / negative regulation of nitric oxide biosynthetic process / behavioral response to ethanol / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / sensory perception / 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 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / neuropeptide binding / regulation of NMDA receptor activity / G alpha (z) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / 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 / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / photoreceptor outer segment membrane / positive regulation of neurogenesis / G alpha (q) signalling events / negative regulation of cytosolic calcium ion concentration / positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / spectrin binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / alkylglycerophosphoethanolamine phosphodiesterase activity / negative regulation of tumor necrosis factor production / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / photoreceptor outer segment / G-protein alpha-subunit binding / neuropeptide signaling pathway / Endogenous sterols / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / voltage-gated calcium channel activity / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / MECP2 regulates neuronal receptors and channels / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / photoreceptor inner segment / sensory perception of pain / cardiac muscle cell apoptotic process / Transcriptional and post-translational regulation of MITF-M expression and activity 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.22 Å | ||||||||||||
![]() | 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 | ![]()
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![]() | ![]() 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
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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 | ![]() | 38 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 25.3 KB 25.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 122.7 KB | ||
Filedesc metadata | ![]() | 7.4 KB | ||
その他 | ![]() ![]() | 31.2 MB 31.2 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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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: 1.071 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_28907_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_28907_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 |
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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 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Mu-type opioid receptor
分子 | 名称: Mu-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: ![]() |
分子量 | 理論値: 45.518719 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DYKDDDDVDS SAAPTNASNC TDALAYSSCS PAPSPGSWVN LSHLDGNLSD PCGPNRTDLG GRDSLCPPTG SPSMITAITI MALYSIVCV VGLFGNFLVM YVIVRYTKMK TATNIYIFNL ALADALATST LPFQSVNYLM GTWPFGTILC KIVISIDYYN M FTSIWTLC ...文字列: DYKDDDDVDS SAAPTNASNC TDALAYSSCS PAPSPGSWVN LSHLDGNLSD PCGPNRTDLG GRDSLCPPTG SPSMITAITI MALYSIVCV VGLFGNFLVM YVIVRYTKMK TATNIYIFNL ALADALATST LPFQSVNYLM GTWPFGTILC KIVISIDYYN M FTSIWTLC TMSVDRYIAV CHPVKALDFR TPRNAKIINV CNWILSSAIG LPVMFMATTK YRQGSIDCTL TFSHPTWYWE NL LKICVFI FAFIMPVLII TVCYGLMILR LKSVRMLSGS KEKDRNLRRI TRMVLVVVAV FIVCWTPIHI YVIIKALVTI PET TFQTVS WHFCIALGYT NSCLNPVLYA FLDENFKRCF REFCIPTSSN IEQQNSTRIR QNTRDHPSTA NTVDRTNHQH HHHH HHH UniProtKB: Mu-type opioid receptor |
-分子 #2: Beta-endorphin
分子 | 名称: Beta-endorphin / 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: ![]() |
分子量 | 理論値: 3.470022 KDa |
配列 | 文字列: YGGFMTSEKS QTPLVTLFKN AIIKNAYKKG E UniProtKB: Pro-opiomelanocortin |
-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: ![]() |
分子量 | 理論値: 40.445059 KDa |
組換発現 | 生物種: ![]() ![]() |
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 UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-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: ![]() ![]() |
分子量 | 理論値: 39.020664 KDa |
組換発現 | 生物種: ![]() ![]() |
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 UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: ![]() ![]() |
分子量 | 理論値: 7.56375 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFC UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #6: scFv16
分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 26.408492 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SAGGGGSGGG GSGGGGSADI VMTQATSSVP VTPGESVSIS C RSSKSLLH ...文字列: MVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SAGGGGSGGG GSGGGGSADI VMTQATSSVP VTPGESVSIS C RSSKSLLH SNGNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TF GAGTKLE L |
-分子 #7: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 7 / コピー数: 10 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.2 |
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凍結 | 凍結剤: ETHANE |
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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: ![]() |
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 |