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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 | momSalB bound Kappa Opioid Receptor in complex with GoA | |||||||||
マップデータ | deep sharp | |||||||||
試料 |
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キーワード | GPCR / Receptor / Kappa / KOR / Opioid / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報response to acrylamide / dynorphin receptor activity / regulation of saliva secretion / sensory perception of temperature stimulus / positive regulation of eating behavior / adenylate cyclase-inhibiting opioid receptor signaling pathway / negative regulation of luteinizing hormone secretion / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion ...response to acrylamide / dynorphin receptor activity / regulation of saliva secretion / sensory perception of temperature stimulus / positive regulation of eating behavior / adenylate cyclase-inhibiting opioid receptor signaling pathway / negative regulation of luteinizing hormone secretion / G protein-coupled opioid receptor activity / G protein-coupled opioid receptor signaling pathway / positive regulation of dopamine secretion / mu-type opioid receptor binding / positive regulation of potassium ion transmembrane transport / vesicle docking involved in exocytosis / corticotropin-releasing hormone receptor 1 binding / receptor serine/threonine kinase binding / maternal behavior / positive regulation of p38MAPK cascade / sensory perception / neuropeptide binding / G protein-coupled dopamine receptor signaling pathway / eating behavior / regulation of heart contraction / parallel fiber to Purkinje cell synapse / conditioned place preference / estrous cycle / postsynaptic modulation of chemical synaptic transmission / MECP2 regulates neuronal receptors and channels / behavioral response to cocaine / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / T-tubule / sensory perception of pain / axon terminus / muscle contraction / Peptide ligand-binding receptors / sarcoplasmic reticulum / response to nicotine / neuropeptide signaling pathway / locomotory behavior / cellular response to glucose stimulus / response to insulin / negative regulation of insulin secretion / response to estrogen / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / 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 / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / synaptic vesicle membrane / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / cellular response to lipopolysaccharide / retina development in camera-type eye / GTPase binding / cell body / G protein activity / presynaptic membrane / fibroblast proliferation / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / defense response to virus / G alpha (q) signalling events 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: 2.82 Å | |||||||||
データ登録者 | Fay JF / Che T | |||||||||
| 資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2023タイトル: Ligand and G-protein selectivity in the κ-opioid receptor. 著者: Jianming Han / Jingying Zhang / Antonina L Nazarova / Sarah M Bernhard / Brian E Krumm / Lei Zhao / Jordy Homing Lam / Vipin A Rangari / Susruta Majumdar / David E Nichols / Vsevolod Katritch ...著者: Jianming Han / Jingying Zhang / Antonina L Nazarova / Sarah M Bernhard / Brian E Krumm / Lei Zhao / Jordy Homing Lam / Vipin A Rangari / Susruta Majumdar / David E Nichols / Vsevolod Katritch / Peng Yuan / Jonathan F Fay / Tao Che / ![]() 要旨: The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has ...The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects. The initiation of KOR signalling requires the G-family proteins including the conventional (G, G, G, G and G) and nonconventional (G and G) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers-G, G, G and G-using cryo-electron microscopy. The KOR-G-protein complexes are bound to hallucinogenic salvinorins or highly selective KOR agonists. Comparisons of these structures reveal molecular determinants critical for KOR-G-protein interactions as well as key elements governing G-family subtype selectivity and KOR ligand selectivity. Furthermore, the four G-protein subtypes display an intrinsically different binding affinity and allosteric activity on agonist binding at KOR. These results provide insights into the actions of opioids and G-protein-coupling specificity at KOR and establish a foundation to examine the therapeutic potential of pathway-selective agonists of KOR. | |||||||||
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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_27805.map.gz | 78.2 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-27805-v30.xml emd-27805.xml | 26.8 KB 26.8 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_27805.png | 34.4 KB | ||
| Filedesc metadata | emd-27805.cif.gz | 7.5 KB | ||
| その他 | emd_27805_additional_1.map.gz emd_27805_half_map_1.map.gz emd_27805_half_map_2.map.gz | 84.9 MB 84.6 MB 84.6 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-27805 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27805 | 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_27805.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 注釈 | deep sharp | ||||||||||||||||||||||||||||||||||||
| 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: 0.88 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
-追加マップ: bfact sharp
| ファイル | emd_27805_additional_1.map | ||||||||||||
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| 注釈 | bfact sharp | ||||||||||||
| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: halfmap
| ファイル | emd_27805_half_map_1.map | ||||||||||||
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| 注釈 | halfmap | ||||||||||||
| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: half map
| ファイル | emd_27805_half_map_2.map | ||||||||||||
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| 注釈 | half map | ||||||||||||
| 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 : momSalB bound Kappa Opioid Receptor in complex with GoA
| 全体 | 名称: momSalB bound Kappa Opioid Receptor in complex with GoA |
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| 要素 |
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-超分子 #1: momSalB bound Kappa Opioid Receptor in complex with GoA
| 超分子 | 名称: momSalB bound Kappa Opioid Receptor in complex with GoA 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 #1: 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: 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: 37.285734 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW ...文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NAICFFPNGN AF ATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGHDNRVSCL GVT DDGMAV ATGSWDSFLK IWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #2: 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: 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: 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 #3: ScFv16 protein
| 分子 | 名称: ScFv16 protein / 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: ![]() |
| 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 #4: Guanine nucleotide-binding protein G(o) subunit alpha
| 分子 | 名称: Guanine nucleotide-binding protein G(o) subunit alpha 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: 40.081438 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGSTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG AGESGKNTIV KQMKIIHEDG FSGEDVKQYK PVVYSNTIQS LAAIVRAMD TLGIEYGDKE RKADAKMVCD VVSRMEDTEP FSAELLSAMM RLWGDSGIQE CFNRSREYQL NDSAKYYLDS L DRIGAADY ...文字列: MGSTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG AGESGKNTIV KQMKIIHEDG FSGEDVKQYK PVVYSNTIQS LAAIVRAMD TLGIEYGDKE RKADAKMVCD VVSRMEDTEP FSAELLSAMM RLWGDSGIQE CFNRSREYQL NDSAKYYLDS L DRIGAADY QPTEQDILRT RVKTTGIVET HFTFKNLHFR LFDVGAQRSE RKKWIHCFED VTAIIFCVAL SGYDQVLHED ET TNRMHAS LKLFDSICNN KFFIDTSIIL FLNKKDLFGE KIKKSPLTIC FPEYTGPNTY EDAAAYIQAQ FESKNRSPNK EIY CHMTCS TDTNNIQVVF DAVTDIIIAN NLRGCGLY UniProtKB: Guanine nucleotide-binding protein G(o) subunit alpha |
-分子 #5: Kappa-type opioid receptor
| 分子 | 名称: Kappa-type opioid receptor / 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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 34.928555 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: LGSISPAIPV IITAVYSVVF VVGLVGNSLV MFVIIRYTKM KTATNIYIFN LALADALVTT TMPFQSTVYL MNSWPFGDVL CKIVLSIDY YNMFTSIFTL TMMSVDRYIA VCHPVKALDF RTPLKAKIIN ICIWLLSSSV GISAIVLGGT KVREDVDVIE C SLQFPDDD ...文字列: LGSISPAIPV IITAVYSVVF VVGLVGNSLV MFVIIRYTKM KTATNIYIFN LALADALVTT TMPFQSTVYL MNSWPFGDVL CKIVLSIDY YNMFTSIFTL TMMSVDRYIA VCHPVKALDF RTPLKAKIIN ICIWLLSSSV GISAIVLGGT KVREDVDVIE C SLQFPDDD YSWWDLFMKI CVFIFAFVIP VLIIIVCYTL MILRLKSVRL LSGSREKDRN LRRITRLVLV VVAVFVVCWT PI HIFILVE ALGSTSHSTA ALSSYYFCIA LGYTNSSLNP ILYAFLDENF KRCFRDFCFP LKMRMERQST S UniProtKB: Kappa-type opioid receptor |
-分子 #6: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(furan-3-yl)-9-(methoxymeth...
| 分子 | 名称: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(furan-3-yl)-9-(methoxymethoxy)-6a,10b-dimethyl-4,10-dioxododecahydro-2H-naphtho[2,1-c]pyran-7-carboxylate タイプ: ligand / ID: 6 / コピー数: 1 / 式: U99 |
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| 分子量 | 理論値: 434.48 Da |
| Chemical component information | ![]() ChemComp-U99: |
-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
| 緩衝液 | pH: 7.5 |
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| 凍結 | 凍結剤: ETHANE-PROPANE |
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電子顕微鏡法
| 顕微鏡 | FEI TALOS ARCTICA |
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| 撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 3853 / 平均電子線量: 42.7 e/Å2 |
| 電子線 | 加速電圧: 200 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): 2.7 µm / 最小 デフォーカス(公称値): 0.2 µm |
| 実験機器 | ![]() モデル: Talos Arctica / 画像提供: FEI Company |
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コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
米国, 1件
引用




































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解析
FIELD EMISSION GUN
