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データを開く
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基本情報
登録情報 | データベース: EMDB / ID: EMD-20794 | ||||||||||||||||||||||||
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タイトル | Integrin alpha-v beta-8 in complex with latent TGF-beta (Primary map: sharpened. Additional map: unsharpened.) | ||||||||||||||||||||||||
![]() | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iv (Primary map: sharpened. Additional map: unsharpened.) | ||||||||||||||||||||||||
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![]() | glycoprotein / adhesion / signaling / SIGNALING PROTEIN | ||||||||||||||||||||||||
機能・相同性 | ![]() Platelet degranulation / Cell surface interactions at the vascular wall / Molecules associated with elastic fibres / TGF-beta receptor signaling activates SMADs / Syndecan interactions / RUNX3 regulates CDKN1A transcription / RUNX3 regulates p14-ARF / TGFBR3 regulates TGF-beta signaling / Downregulation of TGF-beta receptor signaling / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) ...Platelet degranulation / Cell surface interactions at the vascular wall / Molecules associated with elastic fibres / TGF-beta receptor signaling activates SMADs / Syndecan interactions / RUNX3 regulates CDKN1A transcription / RUNX3 regulates p14-ARF / TGFBR3 regulates TGF-beta signaling / Downregulation of TGF-beta receptor signaling / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / Regulation of RUNX3 expression and activity / ganglioside metabolic process / adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains / positive regulation of microglia differentiation / regulation of interleukin-23 production / branch elongation involved in mammary gland duct branching / positive regulation of primary miRNA processing / columnar/cuboidal epithelial cell maturation / negative regulation of skeletal muscle tissue development / regulation of branching involved in mammary gland duct morphogenesis / regulation of enamel mineralization / regulation of cartilage development / regulation of striated muscle tissue development / regulatory T cell differentiation / tolerance induction to self antigen / regulation of protein import into nucleus / embryonic liver development / extracellular matrix assembly / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of hyaluronan biosynthetic process / type III transforming growth factor beta receptor binding / positive regulation of cardiac muscle cell differentiation / hard palate development / odontoblast differentiation / positive regulation of odontogenesis / Langerhans cell differentiation / integrin alphav-beta8 complex / integrin alphav-beta6 complex / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / extracellular matrix protein binding / opsonin binding / negative regulation of macrophage cytokine production / positive regulation of isotype switching to IgA isotypes / positive regulation of mesenchymal stem cell proliferation / membrane protein intracellular domain proteolysis / positive regulation of receptor signaling pathway via STAT / retina vasculature development in camera-type eye / integrin alphav-beta1 complex / mammary gland branching involved in thelarche / Cross-presentation of particulate exogenous antigens (phagosomes) / bronchiole development / hyaluronan catabolic process / positive regulation of vasculature development / lens fiber cell differentiation / positive regulation of extracellular matrix assembly / ATP biosynthetic process / placenta blood vessel development / Laminin interactions / type II transforming growth factor beta receptor binding / receptor catabolic process / positive regulation of chemotaxis / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / type I transforming growth factor beta receptor binding / entry into host cell by a symbiont-containing vacuole / germ cell migration / alphav-beta3 integrin-PKCalpha complex / negative regulation of biomineral tissue development / phospholipid homeostasis / alphav-beta3 integrin-HMGB1 complex / endoderm development / negative regulation of low-density lipoprotein particle clearance / negative regulation of myoblast differentiation / negative regulation of cell-cell adhesion mediated by cadherin / negative regulation of lipid transport / positive regulation of vascular permeability / regulation of phagocytosis / response to cholesterol / oligodendrocyte development / Elastic fibre formation / negative regulation of interleukin-17 production / alphav-beta3 integrin-IGF-1-IGF1R complex / surfactant homeostasis / deubiquitinase activator activity / phosphate-containing compound metabolic process / transforming growth factor beta binding / positive regulation of small GTPase mediated signal transduction / cartilage development / filopodium membrane / sprouting angiogenesis / extracellular matrix binding / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of fibroblast migration / cell-cell junction organization / aortic valve morphogenesis / apolipoprotein A-I-mediated signaling pathway / negative regulation of ossification / apoptotic cell clearance 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: 3.3 Å | ||||||||||||||||||||||||
![]() | Campbell MG / Cormier A | ||||||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM Reveals Integrin-Mediated TGF-β Activation without Release from Latent TGF-β. 著者: Melody G Campbell / Anthony Cormier / Saburo Ito / Robert I Seed / Andrew J Bondesson / Jianlong Lou / James D Marks / Jody L Baron / Yifan Cheng / Stephen L Nishimura / ![]() 要旨: Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. ...Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. Inhibiting αvβ8-mediated TGF-β activation blocks immunosuppressive regulatory T cell differentiation, which is a potential therapeutic strategy in cancer. Using cryo-electron microscopy, structure-guided mutagenesis, and cell-based assays, we reveal the binding interactions between the entire αvβ8 ectodomain and its intact natural ligand, L-TGF-β, as well as two different inhibitory antibody fragments to understand the structural underpinnings of αvβ8 binding specificity and TGF-β activation. Our studies reveal a mechanism of TGF-β activation where mature TGF-β signals within the confines of L-TGF-β and the release and diffusion of TGF-β are not required. The structural details of this mechanism provide a rational basis for therapeutic strategies to inhibit αvβ8-mediated L-TGF-β activation. | ||||||||||||||||||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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 | ![]() | 1.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.5 KB 21.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 99.6 KB | ||
Filedesc metadata | ![]() | 7.4 KB | ||
その他 | ![]() | 52.1 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 319.7 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 319.3 KB | 表示 | |
XML形式データ | ![]() | 6.5 KB | 表示 | |
CIF形式データ | ![]() | 7.5 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 | ![]() 6ujaMC ![]() 6ujbC ![]() 6ujcC 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 | |
電子顕微鏡画像生データ | ![]() Data size: 1.2 TB Data #1: Unaligned 80-frame movies of αVβ8 integrin bound to latent TGF-β on a holey carbon grid [micrographs - multiframe] Data #2: Dose-weighted aligned micrographs of αVβ8 integrin bound to latent TGF-β on a holey carbon grid [micrographs - single frame] Data #3: Dose-weighted aligned particle stacks of αVβ8 integrin bound to latent TGF-β on a holey carbon grid [picked particles - single frame - processed]) ![]() Data size: 2.2 TB Data #1: Unaligned 80-frame movies of αVβ8 integrin bound to latent TGF-β on a graphene oxide grid [micrographs - multiframe] Data #2: Dose-weighted aligned micrographs of αVβ8 integrin bound to latent TGF-β on a graphene oxide grid [micrographs - single frame] Data #3: Dose-weighted aligned particle stacks of αVβ8 integrin bound to latent TGF-β on a graphene oxide grid [picked particles - single frame - processed]) |
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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 | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iv (Primary map: sharpened. Additional map: unsharpened.) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.345 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: Integrin alpha-v beta-8 in complex with latent TGF-beta,...
ファイル | emd_20794_additional.map | ||||||||||||
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注釈 | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iv (Additional unsharpened 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 : Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 ...
全体 | 名称: Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 (L-TGF-b1) |
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要素 |
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-超分子 #1: Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 ...
超分子 | 名称: Binary complex of Integrin alpha-v beta-8 with Latent TGF-beta-1 (L-TGF-b1) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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分子量 | 理論値: 260 KDa |
-超分子 #2: alpha-v beta-8 integrin
超分子 | 名称: alpha-v beta-8 integrin / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: ![]() |
-超分子 #3: Transforming Growth Factor Beta-1 proprotein
超分子 | 名称: Transforming Growth Factor Beta-1 proprotein / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #3 詳細: LTGFb is a homodimer in the sample, but only a single chain is modeled. |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: Integrin alpha-V
分子 | 名称: Integrin alpha-V / 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: 112.813352 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: FNLDVDSPAE YSGPEGSYFG FAVDFFVPSA SSRMFLLVGA PKANTTQPGI VEGGQVLKCD WSSTRRCQPI EFDATGNRDY AKDDPLEFK SHQWFGASVR SKQDKILACA PLYHWRTEMK QEREPVGTCF LQDGTKTVEY APCRSQDIDA DGQGFCQGGF S IDFTKADR ...文字列: FNLDVDSPAE YSGPEGSYFG FAVDFFVPSA SSRMFLLVGA PKANTTQPGI VEGGQVLKCD WSSTRRCQPI EFDATGNRDY AKDDPLEFK SHQWFGASVR SKQDKILACA PLYHWRTEMK QEREPVGTCF LQDGTKTVEY APCRSQDIDA DGQGFCQGGF S IDFTKADR VLLGGPGSFY WQGQLISDQV AEIVSKYDPN VYSIKYNNQL ATRTAQAIFD DSYLGYSVAV GDFNGDGIDD FV SGVPRAA RTLGMVYIYD GKNMSSLYNF TGEQMAAYFG FSVAATDING DDYADVFIGA PLFMDRGSDG KLQEVGQVSV SLQ RASGDF QTTKLNGFEV FARFGSAIAP LGDLDQDGFN DIAIAAPYGG EDKKGIVYIF NGRSTGLNAV PSQILEGQWA ARSM PPSFG YSMKGATDID KNGYPDLIVG AFGVDRAILY RARPVITVNA GLEVYPSILN QDNKTCSLPG TALKVSCFNV RFCLK ADGK GVLPRKLNFQ VELLLDKLKQ KGAIRRALFL YSRSPSHSKN MTISRGGLMQ CEELIAYLRD ESEFRDKLTP ITIFME YRL DYRTAADTTG LQPILNQFTP ANISRQAHIL LDCGEDNVCK PKLEVSVDSD QKKIYIGDDN PLTLIVKAQN QGEGAYE AE LIVSIPLQAD FIGVVRNNEA LARLSCAFKT ENQTRQVVCD LGNPMKAGTQ LLAGLRFSVH QQSEMDTSVK FDLQIQSS N LFDKVSPVVS HKVDLAVLAA VEIRGVSSPD HVFLPIPNWE HKENPETEED VGPVVQHIYE LRNNGPSSFS KAMLHLQWP YKYNNNTLLY ILHYDIDGPM NCTSDMEINP LRIKISSLQT TEKNDTVAGQ GERDHLITKR DLALSEGDIH TLGCGVAQCL KIVCQVGRL DRGKSAILYV KSLLWTETFM NKENQNHSYS LKSSASFNVI EFPYKNLPIE DITNSTLVTT NVTWGIQPAP M PVPVWVII LAVLAGLLLL AVLVFVMYRM GFFKRVRPPQ EEQEREQLQP HENGEGNSET UniProtKB: Integrin alpha-V |
-分子 #2: Integrin beta-8
分子 | 名称: Integrin beta-8 / 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: 81.276664 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: EDNRCASSNA ASCARCLALG PECGWCVQED FISGGSRSER CDIVSNLISK GCSVDSIEYP SVHVIIPTEN EINTQVTPGE VSIQLRPGA EANFMLKVHP LKKYPVDLYY LVDVSASMHN NIEKLNSVGN DLSRKMAFFS RDFRLGFGSY VDKTVSPYIS I HPERIHNQ ...文字列: EDNRCASSNA ASCARCLALG PECGWCVQED FISGGSRSER CDIVSNLISK GCSVDSIEYP SVHVIIPTEN EINTQVTPGE VSIQLRPGA EANFMLKVHP LKKYPVDLYY LVDVSASMHN NIEKLNSVGN DLSRKMAFFS RDFRLGFGSY VDKTVSPYIS I HPERIHNQ CSDYNLDCMP PHGYIHVLSL TENITEFEKA VHRQKISGNI DTPEGGFDAM LQAAVCESHI GWRKEAKRLL LV MTDQTSH LALDSKLAGI VVPNDGNCHL KNNVYVKSTT MEHPSLGQLS EKLIDNNINV IFAVQGKQFH WYKDLLPLLP GTI AGEIES KAANLNNLVV EAYQKLISEV KVQVENQVQG IYFNITAICP DGSRKPGMEG CRNVTSNDEV LFNVTVTMKK CDVT GGKNY AIIKPIGFNE TAKIHIHRNC SCQCEDNRGP KGKCVDETFL DSKCFQCDEN KCHFDEDQFS SESCKSHKDQ PVCSG RGVC VCGKCSCHKI KLGKVYGKYC EKDDFSCPYH HGNLCAGHGE CEAGRCQCFS GWEGDRCQCP SAAAQHCVNS KGQVCS GRG TCVCGRCECT DPRSIGRFCE HCPTCYTACK ENWNCMQCLH PHNLSQAILD QCKTSCALME QQHYVDQTSE CFSSPSY LR IFFIIFIVTF LIGLLKVLII RQVILQWNSN KIKSSSDYRV SASKKDKLIL QSVCTRAVTY RREKPEEIKM DISKLNAH E TFRCNF UniProtKB: Integrin beta-8 |
-分子 #3: Transforming growth factor beta-1 proprotein
分子 | 名称: Transforming growth factor beta-1 proprotein / 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: 41.434449 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: GPLSTCKTID MELVKRKRIE AIRGQILSKL RLASPPSQGD VPPGPLPEAV LALYNSTRDR VAGESVEPEP EPEADYYAKE VTRVLMVES GNQIYDKFKG TPHSLYMLFN TSELREAVPE PVLLSRAELR LLRLKLKVEQ HVELYQKYSN DSWRYLSNRL L APSDSPEW ...文字列: GPLSTCKTID MELVKRKRIE AIRGQILSKL RLASPPSQGD VPPGPLPEAV LALYNSTRDR VAGESVEPEP EPEADYYAKE VTRVLMVES GNQIYDKFKG TPHSLYMLFN TSELREAVPE PVLLSRAELR LLRLKLKVEQ HVELYQKYSN DSWRYLSNRL L APSDSPEW LSFDVTGVVR QWLTRREAIE GFRLSAHCSC DSKDNTLHVE INGFNSGRRG DLATIHGMNR PFLLLMATPL ER AQHLHSS RHRRALDTNY CFSSTEKNCC VRQLYIDFRK DLGWKWIHEP KGYHANFCLG PCPYIWSLDT QYSKVLALYN QHN PGASAA PCCVPQALEP LPIVYYVGRK PKVEQLSNMI VRSCKCS UniProtKB: Transforming growth factor beta-1 proprotein |
-分子 #6: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 6 / コピー数: 5 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-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: 3 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #8: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 8 / コピー数: 1 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-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: 7.5 |
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グリッド | 材質: GRAPHENE OXIDE |
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 70.0 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 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 43600 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |