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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 | Cryo-EM structure of a pre-dimerized murine IL-12 complete extracellular signaling complex (Class 1). | |||||||||
![]() | Main map: Anisotropy sharpened map of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex (Class 1), used for model refinement in Phenix. Additional map: DeepEMhancer sharpened map. | |||||||||
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![]() | Complex / Cytokine / Receptor / SIGNALING PROTEIN | |||||||||
機能・相同性 | ![]() interleukin-12 beta subunit binding / Interleukin-12 signaling / Interleukin-23 signaling / interleukin-23 receptor binding / Interleukin-35 Signalling / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / T-helper 1 cell activation / natural killer cell activation involved in immune response ...interleukin-12 beta subunit binding / Interleukin-12 signaling / Interleukin-23 signaling / interleukin-23 receptor binding / Interleukin-35 Signalling / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / T-helper 1 cell activation / natural killer cell activation involved in immune response / positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of vascular endothelial growth factor signaling pathway / negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis / cellular response to hydroperoxide / positive regulation of T-helper 1 type immune response / regulation of response to tumor cell / positive regulation of autophagic cell death / DAPK1-calmodulin complex / positive regulation of smooth muscle cell apoptotic process / interleukin-12 receptor binding / natural killer cell activation / T-helper cell differentiation / interleukin-23 receptor complex / defense response to tumor cell / Caspase activation via Dependence Receptors in the absence of ligand / negative regulation of interleukin-17 production / positive regulation of osteoclast differentiation / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / response to UV-B / regulation of NMDA receptor activity / CaM pathway / Cam-PDE 1 activation / positive regulation of natural killer cell proliferation / cytokine receptor activity / positive regulation of granulocyte macrophage colony-stimulating factor production / Sodium/Calcium exchangers / syntaxin-1 binding / Calmodulin induced events / Reduction of cytosolic Ca++ levels / calcium/calmodulin-dependent protein kinase activity / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / positive regulation of T cell differentiation / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / regulation of cardiac muscle cell action potential / Activation of RAC1 downstream of NMDARs / negative regulation of interleukin-10 production / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of activated T cell proliferation / defense response to protozoan / Phase 0 - rapid depolarisation / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of interleukin-17 production / RHO GTPases activate PAKs / cytokine binding / : / Ion transport by P-type ATPases / Long-term potentiation / positive regulation of interleukin-10 production / : / Uptake and function of anthrax toxins / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / DARPP-32 events / detection of calcium ion / extrinsic apoptotic signaling pathway via death domain receptors / regulation of cardiac muscle contraction / regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / immunoglobulin mediated immune response / negative regulation of protein secretion / cellular response to interferon-beta / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / calcium channel inhibitor activity / eNOS activation / coreceptor activity / Protein methylation / positive regulation of autophagy / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum 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: 3.6 Å | |||||||||
![]() | Felix J / Bloch Y / Savvides SN | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23. 著者: Yehudi Bloch / Jan Felix / Romain Merceron / Mathias Provost / Royan Alipour Symakani / Robin De Backer / Elisabeth Lambert / Ahmad R Mehdipour / Savvas N Savvides / ![]() ![]() ![]() ![]() 要旨: Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into ...Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into their complete extracellular assemblies. Furthermore, there is a paucity of structural details describing the IL-12-receptor interaction interfaces, in contrast to IL-23-receptor complexes. Here we report structures of fully assembled mouse IL-12/human IL-23-receptor complexes comprising the complete extracellular segments of the cognate receptors determined by electron cryo-microscopy. The structures reveal key commonalities but also surprisingly diverse features. Most notably, whereas IL-12 and IL-23 both utilize a conspicuously presented aromatic residue on their α-subunit as a hotspot to interact with the N-terminal Ig domain of their high-affinity receptors, only IL-12 juxtaposes receptor domains proximal to the cell membrane. Collectively, our findings will help to complete our understanding of cytokine-mediated assemblies of tall cytokine receptors and will enable a cytokine-specific interrogation of IL-12/IL-23 signaling in physiology and disease. | |||||||||
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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 | ![]() | 301.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 25.2 KB 25.2 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 14.6 KB | 表示 | ![]() |
画像 | ![]() | 92.3 KB | ||
マスクデータ | ![]() | 325 MB | ![]() | |
Filedesc metadata | ![]() | 8 KB | ||
その他 | ![]() ![]() ![]() | 284.1 MB 301.2 MB 301.2 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8odzMC ![]() 8c7mC ![]() 8cr5C ![]() 8cr6C ![]() 8cr8C ![]() 8odxC ![]() 8oe0C ![]() 8oe4C ![]() 8pb1C ![]() 8ppmC 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 ![]() |
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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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注釈 | Main map: Anisotropy sharpened map of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex (Class 1), used for model refinement in Phenix. Additional map: DeepEMhancer sharpened map. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.755 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
-マスク #1
ファイル | ![]() | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: DeepEMhancer sharpened map of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex...
ファイル | emd_16820_additional_1.map | ||||||||||||
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注釈 | DeepEMhancer sharpened map of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex (Class 1), used for model building in Coot and visualization in ChimeraX. | ||||||||||||
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 1 of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex...
ファイル | emd_16820_half_map_1.map | ||||||||||||
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注釈 | Half map 1 of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex (Class 1). | ||||||||||||
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 2 of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex...
ファイル | emd_16820_half_map_2.map | ||||||||||||
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注釈 | Half map 2 of the murine IL12:IL12Rbeta1-DAPK1:IL12Rbeta2-Calmodulin complex (Class 1). | ||||||||||||
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 : Murine IL-12 in complex with mIL-12Rbeta1-DAPK1 and mIL-12Rbeta2-...
全体 | 名称: Murine IL-12 in complex with mIL-12Rbeta1-DAPK1 and mIL-12Rbeta2-Calmodulin. |
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要素 |
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-超分子 #1: Murine IL-12 in complex with mIL-12Rbeta1-DAPK1 and mIL-12Rbeta2-...
超分子 | 名称: Murine IL-12 in complex with mIL-12Rbeta1-DAPK1 and mIL-12Rbeta2-Calmodulin. タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 216 KDa |
-分子 #1: Interleukin-12 subunit alpha
分子 | 名称: Interleukin-12 subunit alpha / 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: ![]() ![]() |
分子量 | 理論値: 25.927496 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: RVIPVSGPAR CLSQSRNLLK TTDDMVKTAR EKLKHYSCTA EDIDHEDITR DQTSTLKTCL PLELHKNESC LATRETSSTT RGSCLPPQK TSLMMTLCLG SIYEDLKMYQ TEFQAINAAL QNHNHQQIIL DKGMLVAIDE LMQSLNHNGE TLRQKPPVGE A DPYRVKMK ...文字列: RVIPVSGPAR CLSQSRNLLK TTDDMVKTAR EKLKHYSCTA EDIDHEDITR DQTSTLKTCL PLELHKNESC LATRETSSTT RGSCLPPQK TSLMMTLCLG SIYEDLKMYQ TEFQAINAAL QNHNHQQIIL DKGMLVAIDE LMQSLNHNGE TLRQKPPVGE A DPYRVKMK LCILLHAFST RVVTINRVMG YLSSAGTSDE VDGGSGGSGL NDIFEAQKIE WHEGRTKHHH HHH UniProtKB: Interleukin-12 subunit alpha |
-分子 #2: Interleukin-12 subunit beta
分子 | 名称: Interleukin-12 subunit beta / 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: ![]() ![]() |
分子量 | 理論値: 35.83732 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MWELEKDVYV VEVDWTPDAP GETVNLTCDT PEEDDITWTS DQRHGVIGSG KTLTITVKEF LDAGQYTCHK GGETLSHSHL LLHKKENGI WSTEILKNFK NKTFLKCEAP NYSGRFTCSW LVQRNMDLKF NIKSSSSSPD SRAVTCGMAS LSAEKVTLDQ R DYEKYSVS ...文字列: MWELEKDVYV VEVDWTPDAP GETVNLTCDT PEEDDITWTS DQRHGVIGSG KTLTITVKEF LDAGQYTCHK GGETLSHSHL LLHKKENGI WSTEILKNFK NKTFLKCEAP NYSGRFTCSW LVQRNMDLKF NIKSSSSSPD SRAVTCGMAS LSAEKVTLDQ R DYEKYSVS CQEDVTCPTA EETLPIELAL EARQQNKYEN YSTSFFIRDI IKPDPPKNLQ MKPLKNSQVE VSWEYPDSWS TP HSYFSLK FFVRIQRKKE KMKETEEGCN QKGAFLVEKT STEVQCKGGN VCVQAQDRYY NSSCSKWACV PCRVRS UniProtKB: Interleukin-12 subunit beta |
-分子 #3: Interleukin-12 receptor subunit beta-1,Death-associated protein k...
分子 | 名称: Interleukin-12 receptor subunit beta-1,Death-associated protein kinase 1 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO / EC番号: non-specific serine/threonine protein kinase |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 63.789156 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: QLGASGPGDG CCVEKTSFPE GASGSPLGPR NLSCYRVSKT DYECSWQYDG PEDNVSHVLW CCFVPPNHTH TGQERCRYFS SGPDRTVQF WEQDGIPVLS KVNFWVESRL GNRTMKSQKI SQYLYNWTKT TPPLGHIKVS QSHRQLRMDW NVSEEAGAEV Q FRRRMPTT ...文字列: QLGASGPGDG CCVEKTSFPE GASGSPLGPR NLSCYRVSKT DYECSWQYDG PEDNVSHVLW CCFVPPNHTH TGQERCRYFS SGPDRTVQF WEQDGIPVLS KVNFWVESRL GNRTMKSQKI SQYLYNWTKT TPPLGHIKVS QSHRQLRMDW NVSEEAGAEV Q FRRRMPTT NWTLGDCGPQ VNSGSGVLGD IRGSMSESCL CPSENMAQEI QIRRRRRLSS GAPGGPWSDW SMPVCVPPEV LP QAKIKFL VEPLNQGGRR RLTMQGQSPQ LAVPEGCRGR PGAQVKKHLV LVRMLSCRCQ AQTSKTVPLG KKLNLSGATY DLN VLAKTR FGRSTIQKWH LPAQELTETR ALNVSVGGNM TSMQWAAQAP GTTYCLEWQP WFQHRNHTHC TLIVPEEEDP AKMV THSWS SKPTLEQEEC YRITVFASKN PKNPMLWATV LSSYYFGGNA SRAGTPRHVS VRNQTGDSVS VEWTASQLST CPGVL TQYV VRCEAEDGAW ESEWLVPPTK TQVTLDGLRS RVMYKVQVRA DTARLPGAWS HPQRFSFEGT GGSGGSGGAA RKKWKQ SVR LISLCQRLS UniProtKB: Interleukin-12 receptor subunit beta-1, Death-associated protein kinase 1 |
-分子 #4: Interleukin-12 receptor subunit beta-2,Calmodulin-1
分子 | 名称: Interleukin-12 receptor subunit beta-2,Calmodulin-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: 85.723344 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: NIDVCKLGTV TVQPAPVIPL GSAANISCSL NPKQGCSHYP SSNELILLKF VNDVLVENLH GKKVHDHTGH SSTFQVTNLS LGMTLFVCK LNCSNSQKKP PVPVCGVEIS VGVAPEPPQN ISCVQEGENG TVACSWNSGK VTYLKTNYTL QLSGPNNLTC Q KQCFSDNR ...文字列: NIDVCKLGTV TVQPAPVIPL GSAANISCSL NPKQGCSHYP SSNELILLKF VNDVLVENLH GKKVHDHTGH SSTFQVTNLS LGMTLFVCK LNCSNSQKKP PVPVCGVEIS VGVAPEPPQN ISCVQEGENG TVACSWNSGK VTYLKTNYTL QLSGPNNLTC Q KQCFSDNR QNCNRLDLGI NLSPDLAESR FIVRVTAIND LGNSSSLPHT FTFLDIVIPL PPWDIRINFL NASGSRGTLQ WE DEGQVVL NQLRYQPLNS TSWNMVNATN AKGKYDLRDL RPFTEYEFQI SSKLHLSGGS WSNWSESLRT RTPEEEPVGI LDI WYMKQD IDYDRQQISL FWKSLNPSEA RGKILHYQVT LQEVTKKTTL QNTTRHTSWT RVIPRTGAWT ASVSAANSKG ASAP THINI VDLCGTGLLA PHQVSAKSEN MDNILVTWQP PKKADSAVRE YIVEWRALQP GSITKFPPHW LRIPPDNMSA LISEN IKPY ICYEIRVHAL SESQGGCSSI RGDSKHKAPV SGPHITAITE KKERLFISWT HIPFPEQRGC ILHYRIYWKE RDSTAQ PEL CEIQYRRSQN SHPISSLQPR VTYVLWMTAV TAAGESPQGN EREFCPQGKA NGTGGSGGSG GLTEEQIAEF KEAFSLF DK DGDGTITTKE LGTVMRSLGQ NPTEAELQDM INEVDADGNG TIDFPEFLTM MARKMKDTDS EEEIREAFRV FDKDGNGY I SAAELRHVMT NLGEKLTDEE VDEMIREADI DGDGQVNYEE FVQMMTAK UniProtKB: Interleukin-12 receptor subunit beta-2, Calmodulin-1 |
-分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 6 / コピー数: 5 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #7: water
分子 | 名称: water / タイプ: ligand / ID: 7 / コピー数: 1 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-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: 7.4 構成要素:
詳細: HEPES-buffered saline (HBS) with added calcium chloride: 25 mM HEPES, pH 7.4, 150 mM NaCl, 5 mM CaCl | ||||||||||||
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グリッド | モデル: Quantifoil R2/1 / 材質: COPPER / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE | ||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 95 % / 装置: LEICA PLUNGER / 詳細: Leica EM GP2, 5 s. blotting time.. |
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電子顕微鏡法
顕微鏡 | JEOL CRYO ARM 300 |
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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: 8145 / 平均露光時間: 3.37 sec. / 平均電子線量: 61.8 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): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 60000 |
試料ステージ | ホルダー冷却材: NITROGEN |
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画像解析
-原子モデル構築 1
精密化 | プロトコル: RIGID BODY FIT |
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得られたモデル | ![]() PDB-8odz: |