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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 | Activation mechanism of CYSLTR2 by C16:0 ceramide | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | GPCR / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報cysteinyl leukotriene receptor activity / leukotriene receptor activity / Leukotriene receptors / LTC4-CYSLTR mediated IL4 production / galanin receptor activity / neuropeptide signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta ...cysteinyl leukotriene receptor activity / leukotriene receptor activity / Leukotriene receptors / LTC4-CYSLTR mediated IL4 production / galanin receptor activity / neuropeptide 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-protein beta-subunit binding / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / 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 / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / immune response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol 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: 2.76 Å | |||||||||
データ登録者 | Wang JL / Ding JH / Sun JP / Yu X | |||||||||
| 資金援助 | 中国, 2件
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引用 | ジャーナル: Nature / 年: 2025タイトル: Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis. 著者: Siting Zhang / Hui Lin / Jiale Wang / Jingyu Rui / Tengwei Wang / Zeyu Cai / Shenming Huang / Yanxiang Gao / Tianfeng Ma / Rui Fan / Rongbo Dai / Zhiqing Li / Yiting Jia / Qiang Chen / ...著者: Siting Zhang / Hui Lin / Jiale Wang / Jingyu Rui / Tengwei Wang / Zeyu Cai / Shenming Huang / Yanxiang Gao / Tianfeng Ma / Rui Fan / Rongbo Dai / Zhiqing Li / Yiting Jia / Qiang Chen / HaoMing He / Jiaai Tan / Shirong Zhu / Rui Gu / Zhigang Dong / Meihong Li / Enmin Xie / Yi Fu / Jingang Zheng / Changtao Jiang / Jinpeng Sun / Wei Kong / ![]() 要旨: Recent evidence has shown that increased levels of circulating long-chain ceramides predict atherosclerotic cardiovascular disease independently of cholesterol. Although targeting ceramide signalling ...Recent evidence has shown that increased levels of circulating long-chain ceramides predict atherosclerotic cardiovascular disease independently of cholesterol. Although targeting ceramide signalling may provide therapeutic benefits beyond the treatment of hypercholesterolaemia, the underlying mechanism by which circulating ceramides aggravate atherosclerotic cardiovascular disease remains elusive. Here we examine whether circulating long-chain ceramides activate membrane G-protein-coupled receptors to exacerbate atherosclerosis. We perform a systematic screen that combines G-protein-signalling quantification, bioinformatic analysis of G-protein-coupled receptor expression and functional examination of NLRP3 inflammasome activation. The results suggest that CYSLTR2 and P2RY6 are potential endogenous receptors of C16:0 ceramide-induced inflammasome activation in both endothelial cells and macrophages. Inhibition of CYSLTR2 and P2RY6 genetically or pharmacologically alleviates ceramide-induced atherosclerosis aggravation. Moreover, increased ceramide levels correlate with the severity of coronary artery disease in patients with varying degrees of renal impairment. Notably, CYSLTR2 and P2RY6 deficiency mitigates chronic-kidney-disease-aggravated atherosclerosis in mice without affecting cholesterol or ceramide levels. Structural analyses of ceramide-CYSLTR2-G complexes reveal that both C16:0 and C20:0 ceramides bind in an inclined channel-like ligand-binding pocket on CYSLTR2. We further reveal an unconventional mechanism underlying ceramide-induced CYSLTR2 activation and the CYSLTR2-G interface. Overall, our study provides structural and molecular mechanisms of how long-chain ceramides initiate transmembrane G and inflammasome signalling through direct binding to CYSLTR2 and P2RY6 receptors. Therefore, blocking these signals may provide a new therapeutic potential to treat atherosclerosis-related diseases. | |||||||||
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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_61472.map.gz | 51.7 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-61472-v30.xml emd-61472.xml | 22.6 KB 22.6 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_61472.png | 121.3 KB | ||
| Filedesc metadata | emd-61472.cif.gz | 7.2 KB | ||
| その他 | emd_61472_half_map_1.map.gz emd_61472_half_map_2.map.gz | 59.4 MB 59.4 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-61472 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-61472 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9jh5MC ![]() 9jh6C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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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_61472.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: 0.82 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
-ハーフマップ: #2
| ファイル | emd_61472_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: #1
| ファイル | emd_61472_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 : C16:0-ceramide-CYSLTR2-Gq
| 全体 | 名称: C16:0-ceramide-CYSLTR2-Gq |
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| 要素 |
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-超分子 #1: C16:0-ceramide-CYSLTR2-Gq
| 超分子 | 名称: C16:0-ceramide-CYSLTR2-Gq / 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: Homo sapiens (ヒト) |
-分子 #1: Cysteinyl leukotriene receptor 2
| 分子 | 名称: Cysteinyl leukotriene receptor 2 / 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: 39.678188 KDa |
| 組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
| 配列 | 文字列: MERKFMSLQP SISVSEMEPN GTFSNNNSRN CTIENFKREF FPIVYLIIFF WGVLGNGLSI YVFLQPYKKS TSVNVFMLNL AISDLLFIS TLPFRADYYL RGSNWIFGDL ACRIMSYSLY VNMYSSIYFL TVLSVVRFLA MVHPFRLLHV TSIRSAWILC G IIWILIMA ...文字列: MERKFMSLQP SISVSEMEPN GTFSNNNSRN CTIENFKREF FPIVYLIIFF WGVLGNGLSI YVFLQPYKKS TSVNVFMLNL AISDLLFIS TLPFRADYYL RGSNWIFGDL ACRIMSYSLY VNMYSSIYFL TVLSVVRFLA MVHPFRLLHV TSIRSAWILC G IIWILIMA SSIMLLDSGS EQNGSVTSCL ELNLYKIAKL QTMNYIALVV GCLLPFFTLS ICYLLIIRVL LKVEVPESGL RV SHRKALT TIIITLIIFF LCFLPYHTLR TVHLTTWKVG LCKDRLHKAL VITLALAAAN ACFNPLLYYF AGENFKDRLK SAL RKGHPQ KAKTKCVFPV SVWLRKETRV UniProtKB: Cysteinyl leukotriene receptor 2 |
-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: 6.504446 KDa |
| 組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
| 配列 | 文字列: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFRE UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #3: scFv16
| 分子 | 名称: scFv16 / 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: 26.640643 KDa |
| 組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
| 配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGSSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGSSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KGS |
-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: 41.724383 KDa |
| 組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTSGIFETK FQVDKVNFHM FDVGAQRDER RKWIQCFNDV TAIIFVVDSS DYNRLQEALN DF KSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRKEFVDIST ASG DGRHIC YPHFTCSVDT ENARRIFNDC KDIILQMNLR EYNLV |
-分子 #5: 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: 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: 39.48916 KDa |
| 組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
| 配列 | 文字列: MHHHHHHLEV LFQGPGSSQS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...文字列: MHHHHHHLEV LFQGPGSSQS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #6: Nb35
| 分子 | 名称: Nb35 / 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: ![]() |
| 分子量 | 理論値: 16.22839 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MKYLLPTAAA GLLLLAAQPA MAMQVQLQES GGGLVQPGGS LRLSCAASGF TFSNYKMNWV RQAPGKGLEW VSDISQSGAS ISYTGSVKG RFTISRDNAK NTLYLQMNSL KPEDTAVYYC ARCPAPFTRD CFDVTSTTYA YRGQGTQVTV SS |
-分子 #7: N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)PALMITAMIDE
| 分子 | 名称: N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)PALMITAMIDE タイプ: ligand / ID: 7 / コピー数: 1 / 式: 16C |
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| 分子量 | 理論値: 537.901 Da |
| Chemical component information | ![]() ChemComp-16C: |
-分子 #8: CHOLESTEROL
| 分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 8 / コピー数: 2 / 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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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 |
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| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | TFS KRIOS |
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| 撮影 | フィルム・検出器のモデル: GATAN K2 IS (4k x 4k) / 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 | 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
| 実験機器 | ![]() モデル: Titan Krios / 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
中国, 2件
引用























Z (Sec.)
Y (Row.)
X (Col.)




































Baculovirus expression vector pFastBac1-HM (ウイルス)


解析
FIELD EMISSION GUN
