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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | Kappa opioid receptor:Galphai protein in complex with inverse agonist JDTic | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | G protein coupled receptor / Opioid receptor / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報response to acrylamide / adenylate cyclase-inhibiting opioid receptor signaling pathway / dynorphin receptor activity / regulation of saliva secretion / negative regulation of luteinizing hormone secretion / sensory perception of temperature stimulus / positive regulation of eating behavior / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion ...response to acrylamide / adenylate cyclase-inhibiting opioid receptor signaling pathway / dynorphin receptor activity / regulation of saliva secretion / negative regulation of luteinizing hormone secretion / sensory perception of temperature stimulus / positive regulation of eating behavior / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion / sensory perception / maternal behavior / positive regulation of potassium ion transmembrane transport / receptor serine/threonine kinase binding / neuropeptide binding / positive regulation of p38MAPK cascade / eating behavior / conditioned place preference / neuropeptide signaling pathway / estrous cycle / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / behavioral response to cocaine / MECP2 regulates neuronal receptors and channels / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / axon terminus / sensory perception of pain / T-tubule / cellular response to forskolin / regulation of mitotic spindle organization / Peptide ligand-binding receptors / sarcoplasmic reticulum / response to nicotine / Regulation of insulin secretion / locomotory behavior / cellular response to glucose stimulus / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / response to insulin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / response to estrogen / 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-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / synaptic vesicle membrane / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / cellular response to lipopolysaccharide / presynaptic membrane / GTPase binding / Ca2+ pathway / fibroblast proliferation / midbody 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() | |||||||||
| 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 | Gati C / Motiwala Z / Tyson AS / Styrpejko D / Han GW / Khan S / Ramos-Gonzalez N / Shenvi R / Majumdar S | |||||||||
| 資金援助 | 米国, 2件
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引用 | ジャーナル: Nat Chem Biol / 年: 2025タイトル: Molecular mechanisms of inverse agonism via κ-opioid receptor-G protein complexes. 著者: Aaliyah S Tyson / Saif Khan / Zenia Motiwala / Gye Won Han / Zixin Zhang / Mohsen Ranjbar / Daniel Styrpejko / Nokomis Ramos-Gonzalez / Stone Woo / Kelly Villers / Delainey Landaker / Terry ...著者: Aaliyah S Tyson / Saif Khan / Zenia Motiwala / Gye Won Han / Zixin Zhang / Mohsen Ranjbar / Daniel Styrpejko / Nokomis Ramos-Gonzalez / Stone Woo / Kelly Villers / Delainey Landaker / Terry Kenakin / Ryan Shenvi / Susruta Majumdar / Cornelius Gati / ![]() 要旨: Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex ...Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist. The pharmacological impact of agonist-free receptor-G protein complexes is poorly understood. Here we present biochemical evidence that certain κ-opioid receptor (KOR) inverse agonists can act via KOR-G protein complexes. To investigate this phenomenon, we determined cryo-EM structures of KOR-G protein complexes with three inverse agonists: JDTic, norBNI and GB18, corresponding to structures of inverse agonist-bound GPCR-G protein complexes. Remarkably, the orthosteric binding pocket resembles the G protein-free 'inactive' receptor conformation, while the receptor remains coupled to the G protein. In summary, our work challenges the canonical model of receptor antagonism and offers crucial insights into GPCR pharmacology. | |||||||||
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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 | emd_43557.map.gz | 59.6 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-43557-v30.xml emd-43557.xml | 23.5 KB 23.5 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_43557.png | 72.2 KB | ||
| Filedesc metadata | emd-43557.cif.gz | 7.8 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-43557 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43557 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_43557_validation.pdf.gz | 469.6 KB | 表示 | EMDB検証レポート |
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| 文書・詳細版 | emd_43557_full_validation.pdf.gz | 469.2 KB | 表示 | |
| XML形式データ | emd_43557_validation.xml.gz | 6 KB | 表示 | |
| CIF形式データ | emd_43557_validation.cif.gz | 7 KB | 表示 | |
| アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43557 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43557 | HTTPS FTP |
-関連構造データ
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_43557.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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| 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: 1.294 Å | ||||||||||||||||||||||||||||||||||||
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
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試料の構成要素
-全体 : Kappa opioid receptor in complex with heterotrimeric G protein (G...
| 全体 | 名称: Kappa opioid receptor in complex with heterotrimeric G protein (Gai/b/g) and inverse agonist JDTic |
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| 要素 |
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-超分子 #1: Kappa opioid receptor in complex with heterotrimeric G protein (G...
| 超分子 | 名称: Kappa opioid receptor in complex with heterotrimeric G protein (Gai/b/g) and inverse agonist JDTic タイプ: complex / ID: 1 / 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) |
| 分子量 | 理論値: 130 kDa/nm |
-分子 #1: Kappa-type opioid receptor
| 分子 | 名称: Kappa-type opioid receptor / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 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: 42.68102 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MDSPIQIFRG EPGPTCAPSA CLPPNSSAWF PGWAEPDSNG SAGSEDAQLE PAHISPAIPV IITAVYSVVF VVGLVGNSLV MFVIIRYTK MKTATNIYIF NLALADALVT TTMPFQSTVY LMNSWPFGDV LCKIVISIDY YNMFTSIFTL TMMSVDRYIA V CHPVKALD ...文字列: MDSPIQIFRG EPGPTCAPSA CLPPNSSAWF PGWAEPDSNG SAGSEDAQLE PAHISPAIPV IITAVYSVVF VVGLVGNSLV MFVIIRYTK MKTATNIYIF NLALADALVT TTMPFQSTVY LMNSWPFGDV LCKIVISIDY YNMFTSIFTL TMMSVDRYIA V CHPVKALD FRTPLKAKII NICIWLLSSS VGISAIVLGG TKVREDVDVI ECSLQFPDDD YSWWDLFMKI CVFIFAFVIP VL IIIVCYT LMILRLKSVR LLSGSREKDR NLRRITRLVL VVVAVFVVCW TPIHIFILVE ALGSTSHSTA ALSSYYFCIA LGY TNSSLN PILYAFLDEN FKRCFRDFCF PLKMRMERQS TSRVRNTVQD PAYLRDIDGM NKPV UniProtKB: Kappa-type opioid receptor |
-分子 #2: 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: 2 / コピー数: 1 / 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: 37.41693 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: 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 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 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: 7.861143 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: 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: 4 / コピー数: 1 / 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: 40.415031 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 FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #5: scFv16
| 分子 | 名称: scFv16 / 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: 26.679721 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAA |
-分子 #6: (3R)-7-hydroxy-N-{(2S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethy...
| 分子 | 名称: (3R)-7-hydroxy-N-{(2S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]-3-methylbutan-2-yl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide タイプ: ligand / ID: 6 / コピー数: 1 / 式: JDC |
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| 分子量 | 理論値: 465.628 Da |
| Chemical component information | ![]() ChemComp-JDC: |
-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 |
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試料調製
| 濃度 | 18 mg/mL | ||||||||||||
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| 緩衝液 | pH: 7.5 構成要素:
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| グリッド | モデル: Quantifoil / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY ARRAY / 前処理 - タイプ: GLOW DISCHARGE | ||||||||||||
| 凍結 | 凍結剤: ETHANE / チャンバー内湿度: 90 % / チャンバー内温度: 298 K / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
| 顕微鏡 | FEI TITAN KRIOS |
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| 特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 20 eV |
| 撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 平均電子線量: 60.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | C2レンズ絞り径: 50.0 µm / 倍率(補正後): 105000 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): -25.0 µm / 最小 デフォーカス(公称値): -15.0 µm |
| 試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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万見について




キーワード
Homo sapiens (ヒト)
データ登録者
米国, 2件
引用











































Z (Sec.)
Y (Row.)
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解析
FIELD EMISSION GUN
