+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-16822 | |||||||||
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タイトル | Cryo-EM structure of the murine IL-12 complete extracellular signaling complex (Class 1). | |||||||||
マップデータ | Sharpened map of the murine IL12:IL12Rbeta1:IL12Rbeta2 complex (Class 1). | |||||||||
試料 |
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キーワード | Complex / Cytokine / Receptor / SIGNALING PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 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 / positive regulation of T-helper 1 type immune response / positive regulation of smooth muscle cell apoptotic process / interleukin-12 receptor binding / natural killer cell activation / T-helper cell differentiation / interleukin-23 receptor complex / 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 / cytokine receptor activity / positive regulation of natural killer cell proliferation / positive regulation of granulocyte macrophage colony-stimulating factor production / positive regulation of T cell differentiation / negative regulation of interleukin-10 production / positive regulation of activated T cell proliferation / defense response to protozoan / positive regulation of interleukin-17 production / cytokine binding / positive regulation of interleukin-10 production / : / immunoglobulin mediated immune response / negative regulation of protein secretion / coreceptor activity / T cell proliferation / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of defense response to virus by host / negative regulation of inflammatory response to antigenic stimulus / positive regulation of interleukin-12 production / negative regulation of smooth muscle cell proliferation / response to cytokine / cytokine activity / endosome lumen / growth factor activity / cellular response to type II interferon / cytokine-mediated signaling pathway / Golgi lumen / positive regulation of T cell mediated cytotoxicity / positive regulation of type II interferon production / positive regulation of tumor necrosis factor production / cell migration / cellular response to lipopolysaccharide / defense response to virus / defense response to Gram-negative bacterium / receptor complex / cell population proliferation / response to lipopolysaccharide / cell surface receptor signaling pathway / immune response / protein heterodimerization activity / endoplasmic reticulum lumen / external side of plasma membrane / protein-containing complex binding / protein kinase binding / cell surface / extracellular space / extracellular region / identical protein binding / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Mus musculus (ハツカネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 5.6 Å | |||||||||
データ登録者 | Felix J / Bloch Y / Savvides SN | |||||||||
資金援助 | ベルギー, 2件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2024 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 | emd_16822.map.gz | 38.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-16822-v30.xml emd-16822.xml | 20.8 KB 20.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_16822_fsc.xml | 7.3 KB | 表示 | FSCデータファイル |
画像 | emd_16822.png | 78.8 KB | ||
マスクデータ | emd_16822_msk_1.map | 40.6 MB | マスクマップ | |
Filedesc metadata | emd-16822.cif.gz | 6.6 KB | ||
その他 | emd_16822_half_map_1.map.gz emd_16822_half_map_2.map.gz | 37.7 MB 37.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-16822 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16822 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_16822_validation.pdf.gz | 827 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_16822_full_validation.pdf.gz | 826.6 KB | 表示 | |
XML形式データ | emd_16822_validation.xml.gz | 14.6 KB | 表示 | |
CIF形式データ | emd_16822_validation.cif.gz | 18.3 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16822 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16822 | HTTPS FTP |
-関連構造データ
-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 |
-マップ
ファイル | ダウンロード / ファイル: emd_16822.map.gz / 形式: CCP4 / 大きさ: 40.6 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Sharpened map of the murine IL12:IL12Rbeta1:IL12Rbeta2 complex (Class 1). | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.51 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 | emd_16822_msk_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: Half map 2 of the murine IL12:IL12Rbeta1:IL12Rbeta2 complex...
ファイル | emd_16822_half_map_1.map | ||||||||||||
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注釈 | Half map 2 of the murine IL12:IL12Rbeta1:IL12Rbeta2 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 1 of the murine IL12:IL12Rbeta1:IL12Rbeta2 complex...
ファイル | emd_16822_half_map_2.map | ||||||||||||
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注釈 | Half map 1 of the murine IL12:IL12Rbeta1:IL12Rbeta2 complex (Class 1). | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Murine IL-12 in complex with Strep-II tagged mIL-12Rbeta1 and mIL...
全体 | 名称: Murine IL-12 in complex with Strep-II tagged mIL-12Rbeta1 and mIL-12Rbeta2. |
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要素 |
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-超分子 #1: Murine IL-12 in complex with Strep-II tagged mIL-12Rbeta1 and mIL...
超分子 | 名称: Murine IL-12 in complex with Strep-II tagged mIL-12Rbeta1 and mIL-12Rbeta2. タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 198 KDa |
-分子 #1: Murine Interleukin-12 subunit alpha (IL-12A, p35), with a C-termi...
分子 | 名称: Murine Interleukin-12 subunit alpha (IL-12A, p35), with a C-terminal caspase-3 cleavable His tag. タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MCQSRYLLFL ATLALLNHLS LARVIPVSGP ARCLSQSRNL LKTTDDMVKT AREKLKHYSC TAEDIDHEDI TRDQTSTLKT CLPLELHKNE SCLATRETSS TTRGSCLPPQ KTSLMMTLCL GSIYEDLKMY QTEFQAINAA LQNHNHQQII LDKGMLVAID ELMQSLNHNG ...文字列: MCQSRYLLFL ATLALLNHLS LARVIPVSGP ARCLSQSRNL LKTTDDMVKT AREKLKHYSC TAEDIDHEDI TRDQTSTLKT CLPLELHKNE SCLATRETSS TTRGSCLPPQ KTSLMMTLCL GSIYEDLKMY QTEFQAINAA LQNHNHQQII LDKGMLVAID ELMQSLNHNG ETLRQKPPVG EADPYRVKMK LCILLHAFST RVVTINRVMG YLSSAGTSDE VDGGSGGSGL NDIFEAQKIE WHEGRTKHHH HHH UniProtKB: Interleukin-12 subunit alpha |
-分子 #2: Murine Interleukin-12 subunit beta (IL-12B, p40).
分子 | 名称: Murine Interleukin-12 subunit beta (IL-12B, p40). / タイプ: protein_or_peptide / ID: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MCPQKLTISW FAIVLLVSPL MAMWELEKDV YVVEVDWTPD APGETVNLTC DTPEEDDITW TSDQRHGVIG SGKTLTITVK EFLDAGQYTC HKGGETLSHS HLLLHKKENG IWSTEILKNF KNKTFLKCEA PNYSGRFTCS WLVQRNMDLK FNIKSSSSSP DSRAVTCGMA ...文字列: MCPQKLTISW FAIVLLVSPL MAMWELEKDV YVVEVDWTPD APGETVNLTC DTPEEDDITW TSDQRHGVIG SGKTLTITVK EFLDAGQYTC HKGGETLSHS HLLLHKKENG IWSTEILKNF KNKTFLKCEA PNYSGRFTCS WLVQRNMDLK FNIKSSSSSP DSRAVTCGMA SLSAEKVTLD QRDYEKYSVS CQEDVTCPTA EETLPIELAL EARQQNKYEN YSTSFFIRDI IKPDPPKNLQ MKPLKNSQVE VSWEYPDSWS TPHSYFSLKF FVRIQRKKEK MKETEEGCNQ KGAFLVEKTS TEVQCKGGNV CVQAQDRYYN SSCSKWACVP CRVRS UniProtKB: Interleukin-12 subunit beta |
-分子 #3: Murine Interleukin-12 Receptor beta 1 (domains 1 to 5) with C-ter...
分子 | 名称: Murine Interleukin-12 Receptor beta 1 (domains 1 to 5) with C-terminal Strep-II tag. タイプ: protein_or_peptide / ID: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: QLGASGPGDG CCVEKTSFPE GASGSPLGPR NLSCYRVSKT DYECSWQYDG PEDNVSHVLW CCFVPPNHTH TGQERCRYFS SGPDRTVQFW EQDGIPVLSK VNFWVESRLG NRTMKSQKIS QYLYNWTKTT PPLGHIKVSQ SHRQLRMDWN VSEEAGAEVQ FRRRMPTTNW ...文字列: QLGASGPGDG CCVEKTSFPE GASGSPLGPR NLSCYRVSKT DYECSWQYDG PEDNVSHVLW CCFVPPNHTH TGQERCRYFS SGPDRTVQFW EQDGIPVLSK VNFWVESRLG NRTMKSQKIS QYLYNWTKTT PPLGHIKVSQ SHRQLRMDWN VSEEAGAEVQ FRRRMPTTNW TLGDCGPQVN SGSGVLGDIR GSMSESCLCP SENMAQEIQI RRRRRLSSGA PGGPWSDWSM PVCVPPEVLP QAKIKFLVEP LNQGGRRRLT MQGQSPQLAV PEGCRGRPGA QVKKHLVLVR MLSCRCQAQT SKTVPLGKKL NLSGATYDLN VLAKTRFGRS TIQKWHLPAQ ELTETRALNV SVGGNMTSMQ WAAQAPGTTY CLEWQPWFQH RNHTHCTLIV PEEEDPAKMV THSWSSKPTL EQEECYRITV FASKNPKNPM LWATVLSSYY FGGNASRAGT PRHVSVRNQT GDSVSVEWTA SQLSTCPGVL TQYVVRCEAE DGAWESEWLV PPTKTQVTLD GLRSRVMYKV QVRADTARLP GAWSHPQRFS FEGTWSHPQF EK UniProtKB: Interleukin-12 receptor subunit beta-1 |
-分子 #4: Murine Interleukin-12 Receptor beta 2 (domains 1 to 6) with C-ter...
分子 | 名称: Murine Interleukin-12 Receptor beta 2 (domains 1 to 6) with C-terminal Strep-II tag. タイプ: protein_or_peptide / ID: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: NIDVCKLGTV TVQPAPVIPL GSAANISCSL NPKQGCSHYP SSNELILLKF VNDVLVENLH GKKVHDHTGH SSTFQVTNLS LGMTLFVCKL NCSNSQKKPP VPVCGVEISV GVAPEPPQNI SCVQEGENGT VACSWNSGKV TYLKTNYTLQ LSGPNNLTCQ KQCFSDNRQN ...文字列: NIDVCKLGTV TVQPAPVIPL GSAANISCSL NPKQGCSHYP SSNELILLKF VNDVLVENLH GKKVHDHTGH SSTFQVTNLS LGMTLFVCKL NCSNSQKKPP VPVCGVEISV GVAPEPPQNI SCVQEGENGT VACSWNSGKV TYLKTNYTLQ LSGPNNLTCQ KQCFSDNRQN CNRLDLGINL SPDLAESRFI VRVTAINDLG NSSSLPHTFT FLDIVIPLPP WDIRINFLNA SGSRGTLQWE DEGQVVLNQL RYQPLNSTSW NMVNATNAKG KYDLRDLRPF TEYEFQISSK LHLSGGSWSN WSESLRTRTP EEEPVGILDI WYMKQDIDYD RQQISLFWKS LNPSEARGKI LHYQVTLQEV TKKTTLQNTT RHTSWTRVIP RTGAWTASVS AANSKGASAP THINIVDLCG TGLLAPHQVS AKSENMDNIL VTWQPPKKAD SAVREYIVEW RALQPGSITK FPPHWLRIPP DNMSALISEN IKPYICYEIR VHALSESQGG CSSIRGDSKH KAPVSGPHIT AITEKKERLF ISWTHIPFPE QRGCILHYRI YWKERDSTAQ PELCEIQYRR SQNSHPISSL QPRVTYVLWM TAVTAAGESP QGNEREFCPQ GKANGTWSHP QFEK UniProtKB: Interleukin-12 receptor subunit beta-2 |
-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 |
-試料調製
緩衝液 | pH: 7.4 構成要素:
詳細: HEPES-buffered saline (HBS): 25 mM HEPES, pH 7.4, 150 mM NaCl. | |||||||||
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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 s. blotting time.. |
-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: 7174 / 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: 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): 2.5 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 |