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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 human IL-23 complete extracellular signaling complex. | |||||||||
![]() | Main map: Unfiltered, non-sharpened map of the human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex 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 | ![]() late endosome lumen / interleukin-23-mediated signaling pathway / regulation of tyrosine phosphorylation of STAT protein / interleukin-23 receptor binding / interleukin-27 receptor activity / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / natural killer cell activation involved in immune response / positive regulation of natural killer cell activation ...late endosome lumen / interleukin-23-mediated signaling pathway / regulation of tyrosine phosphorylation of STAT protein / interleukin-23 receptor binding / interleukin-27 receptor activity / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / natural killer cell activation involved in immune response / positive regulation of natural killer cell activation / positive regulation of lymphocyte proliferation / 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 / positive regulation of tissue remodeling / cellular response to hydroperoxide / positive regulation of activation of Janus kinase activity / tissue remodeling / sexual reproduction / 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 NK T cell activation / positive regulation of smooth muscle cell apoptotic process / positive regulation of mononuclear cell proliferation / interleukin-12 receptor binding / positive regulation of memory T cell differentiation / interleukin-12 receptor complex / natural killer cell activation / T-helper cell differentiation / interleukin-23 receptor complex / defense response to tumor cell / positive regulation of osteoclast differentiation / Interleukin-23 signaling / Caspase activation via Dependence Receptors in the absence of ligand / negative regulation of interleukin-17 production / positive regulation of T-helper 17 type immune response / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / positive regulation of neutrophil chemotaxis / Interleukin-12 signaling / response to UV-B / regulation of NMDA receptor activity / CaM pathway / Cam-PDE 1 activation / positive regulation of natural killer cell proliferation / 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 / Loss of phosphorylation of MECP2 at T308 / cytokine receptor activity / 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 / T-helper 1 type immune response / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / 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 / positive regulation of activated T cell proliferation / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / defense response to protozoan / response to type II interferon / Phase 0 - rapid depolarisation / positive regulation of interleukin-17 production / cytokine binding / protein phosphatase activator activity / RHO GTPases activate PAKs / Interleukin-10 signaling / positive regulation of phosphoprotein phosphatase activity / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / Ion transport by P-type ATPases / Long-term potentiation / positive regulation of interleukin-10 production / Uptake and function of anthrax toxins / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / catalytic complex / positive regulation of cell adhesion / DARPP-32 events / detection of calcium ion / extrinsic apoptotic signaling pathway via death domain receptors 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 | |||||||||
![]() | Bloch Y / Felix J / 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. | |||||||||
履歴 |
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構造の表示
添付画像 |
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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 | ![]() | 116.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 24.7 KB 24.7 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 10.6 KB | 表示 | ![]() |
画像 | ![]() | 72.8 KB | ||
マスクデータ | ![]() | 125 MB | ![]() | |
Filedesc metadata | ![]() | 7.7 KB | ||
その他 | ![]() ![]() ![]() | 107.7 MB 116.1 MB 116.1 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 924.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 924.4 KB | 表示 | |
XML形式データ | ![]() | 18.4 KB | 表示 | |
CIF形式データ | ![]() | 24.3 KB | 表示 | |
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 | ![]() 8oe4MC ![]() 8c7mC ![]() 8cr5C ![]() 8cr6C ![]() 8cr8C ![]() 8odxC ![]() 8odzC ![]() 8oe0C ![]() 8pb1C ![]() 8ppmC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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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: Unfiltered, non-sharpened map of the human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex used for model refinement in Phenix. Additional map: deepEMhancer sharpened map. | ||||||||||||||||||||||||||||||||||||
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: 0.9815 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 human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex,...
ファイル | emd_16824_additional_1.map | ||||||||||||
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注釈 | DeepEMhancer sharpened map of the human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex, used for model building in Coot and visualization. | ||||||||||||
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 human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex....
ファイル | emd_16824_half_map_1.map | ||||||||||||
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注釈 | Half map 2 of the human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex. | ||||||||||||
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 human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex....
ファイル | emd_16824_half_map_2.map | ||||||||||||
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注釈 | Half map 1 of the human IL23:IL12Rbeta1-DAPK1:IL23R-Calmodulin complex. | ||||||||||||
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 : Human IL-23 in complex with hIL-12Rbeta1-DAPK1 and hIL-23R-Calmodulin.
全体 | 名称: Human IL-23 in complex with hIL-12Rbeta1-DAPK1 and hIL-23R-Calmodulin. |
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要素 |
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-超分子 #1: Human IL-23 in complex with hIL-12Rbeta1-DAPK1 and hIL-23R-Calmodulin.
超分子 | 名称: Human IL-23 in complex with hIL-12Rbeta1-DAPK1 and hIL-23R-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: 168 KDa |
-分子 #1: Interleukin-12 subunit beta
分子 | 名称: Interleukin-12 subunit beta / タイプ: protein_or_peptide / ID: 1 詳細: N-glycosylation mutant: Asparagine 303 (N303) is mutated to Aspartic acid (D303). 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: 34.74093 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: IWELKKDVYV VELDWYPDAP GEMVVLTCDT PEEDGITWTL DQSSEVLGSG KTLTIQVKEF GDAGQYTCHK GGEVLSHSLL LLHKKEDGI WSTDILKDQK EPKNKTFLRC EAKNYSGRFT CWWLTTISTD LTFSVKSSRG SSDPQGVTCG AATLSAERVR G DNKEYEYS ...文字列: IWELKKDVYV VELDWYPDAP GEMVVLTCDT PEEDGITWTL DQSSEVLGSG KTLTIQVKEF GDAGQYTCHK GGEVLSHSLL LLHKKEDGI WSTDILKDQK EPKNKTFLRC EAKNYSGRFT CWWLTTISTD LTFSVKSSRG SSDPQGVTCG AATLSAERVR G DNKEYEYS VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN LQLKPLKNSR QVEVSWEYPD TW STPHSYF SLTFCVQVQG KSKREKKDRV FTDKTSATVI CRKDASISVR AQDRYYSSSW SEWASVPCS UniProtKB: Interleukin-12 subunit beta |
-分子 #2: Interleukin-23 subunit alpha
分子 | 名称: Interleukin-23 subunit alpha / 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: 20.650117 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: RAVPGGSSPA WTQCQQLSQK LCTLAWSAHP LVGHMDLREE GDEETTNDVP HIQCGDGCDP QGLRDNSQFC LQRIHQGLIF YEKLLGSDI FTGEPSLLPD SPVGQLHASL LGLSQLLQPE GHHWETQQIP SLSPSQPWQR LLLRFKILRS LQAFVAVAAR V FAHGAATL SPGDEVDGHH HHHHHHHH UniProtKB: Interleukin-23 subunit alpha |
-分子 #3: Interleukin-23 receptor,Calmodulin-1
分子 | 名称: Interleukin-23 receptor,Calmodulin-1 / 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: 54.991391 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: GITNINCSGH IWVEPATIFK MGMNISIYCQ AAIKNCQPRK LHFYKNGIKE RFQITRINKT TARLWYKNFL EPHASMYCTA ECPKHFQET LICGKDISSG YPPDIPDEVT CVIYEYSGNM TCTWNAGKLT YIDTKYVVHV KSLETEEEQQ YLTSSYINIS T DSLQGGKK ...文字列: GITNINCSGH IWVEPATIFK MGMNISIYCQ AAIKNCQPRK LHFYKNGIKE RFQITRINKT TARLWYKNFL EPHASMYCTA ECPKHFQET LICGKDISSG YPPDIPDEVT CVIYEYSGNM TCTWNAGKLT YIDTKYVVHV KSLETEEEQQ YLTSSYINIS T DSLQGGKK YLVWVQAANA LGMEESKQLQ IHLDDIVIPS AAVISRAETI NATVPKTIIY WDSQTTIEKV SCEMRYKATT NQ TWNVKEF DTNFTYVQQS EFYLEPNIKY VFQVRCQETG KRYWQPWSSL FFHKTPETVP QVTSKAFQHD TWNSGLTVAS IST GHLTSD NRGDGTGGSG GSGGLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTI DFPEF LTMMARKMKD TDSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQ MMTA K UniProtKB: Interleukin-23 receptor, Calmodulin-1 |
-分子 #4: 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: 4 / 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: 60.187316 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: CRTSECCFQD PPYPDADSGS ASGPRDLRCY RISSDRYECS WQYEGPTAGV SHFLRCCLSS GRCCYFAAGS ATRLQFSDQA GVSVLYTVT LWVESWARNQ TEKSPEVTLQ LYNSVKYEPP LGDIKVSKLA GQLRMEWETP DNQVGAEVQF RHRTPSSPWK L GDCGPQDD ...文字列: CRTSECCFQD PPYPDADSGS ASGPRDLRCY RISSDRYECS WQYEGPTAGV SHFLRCCLSS GRCCYFAAGS ATRLQFSDQA GVSVLYTVT LWVESWARNQ TEKSPEVTLQ LYNSVKYEPP LGDIKVSKLA GQLRMEWETP DNQVGAEVQF RHRTPSSPWK L GDCGPQDD DTESCLCPLE MNVAQEFQLR RRQLGSQGSS WSKWSSPVCV PPENPPQPQV RFSVEQLGQD GRRRLTLKEQ PT QLELPEG CQGLAPGTEV TYRLQLHMLS CPCKAKATRT LHLGKMPYLS GAAYNVAVIS SNQFGPGLNQ TWHIPADTHT EPV ALNISV GTNGTTMYWP ARAQSMTYCI EWQPVGQDGG LATCSLTAPQ DPDPAGMATY SWSRESGAMG QEKCYYITIF ASAH PEKLT LWSTVLSTYH FGGNASAAGT PHHVSVKNHS LDSVSVDWAP SLLSTCPGVL KEYVVRCRDE DSKQVSEHPV QPTET QVTL SGLRAGVAYT VQVRADTAWL RGVWSQPQRF SIEGTGGSGG SGGAARKKWK QSVRLISLCQ RLS UniProtKB: Interleukin-12 receptor subunit beta-1, Death-associated protein kinase 1 |
-分子 #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 7 / コピー数: 2 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-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, 4.5 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: 6660 / 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-8oe4: |