+データを開く
-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.) | ||||||||||||||||||||||||
マップデータ | Integrin alpha-v beta-8 in complex with latent TGF-beta, Conformation iv (Primary map: sharpened. Additional map: unsharpened.) | ||||||||||||||||||||||||
試料 |
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キーワード | glycoprotein / adhesion / signaling / SIGNALING PROTEIN | ||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 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 / positive regulation of microglia differentiation / negative regulation of skeletal muscle tissue development / regulation of striated muscle tissue development / regulation of protein import into nucleus / negative regulation of hyaluronan biosynthetic process / type III transforming growth factor beta receptor binding / Langerhans cell differentiation / extracellular matrix assembly / integrin alphav-beta8 complex / integrin alphav-beta6 complex / hard palate development / transforming growth factor beta production / odontoblast differentiation / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / opsonin binding / negative regulation of macrophage cytokine production / positive regulation of isotype switching to IgA isotypes / integrin alphav-beta1 complex / Cross-presentation of particulate exogenous antigens (phagosomes) / membrane protein intracellular domain proteolysis / extracellular matrix protein binding / hyaluronan catabolic process / Laminin interactions / ATP biosynthetic process / receptor catabolic process / placenta blood vessel development / negative regulation of lipoprotein metabolic process / integrin alphav-beta3 complex / negative regulation of low-density lipoprotein receptor activity / type II transforming growth factor beta receptor binding / alphav-beta3 integrin-PKCalpha complex / alphav-beta3 integrin-HMGB1 complex / type I transforming growth factor beta receptor binding / regulation of phagocytosis / positive regulation of chemotaxis / negative regulation of lipid transport / negative regulation of myoblast differentiation / cell-cell junction organization / Elastic fibre formation / alphav-beta3 integrin-IGF-1-IGF1R complex / response to cholesterol / transforming growth factor beta binding / entry into host cell by a symbiont-containing vacuole / positive regulation of small GTPase mediated signal transduction / filopodium membrane / extracellular matrix binding / phosphate-containing compound metabolic process / positive regulation of fibroblast migration / apolipoprotein A-I-mediated signaling pathway / apoptotic cell clearance / cartilage development / wound healing, spreading of epidermal cells / integrin complex / heterotypic cell-cell adhesion / positive regulation of intracellular signal transduction / Molecules associated with elastic fibres / cell adhesion mediated by integrin / positive regulation of epidermal growth factor receptor signaling pathway / microvillus membrane / negative chemotaxis / Syndecan interactions / negative regulation of cell-cell adhesion / cell-substrate adhesion / negative regulation of fat cell differentiation / endodermal cell differentiation / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / positive regulation of interleukin-17 production / PECAM1 interactions / positive regulation of cell division / positive regulation of SMAD protein signal transduction / lamellipodium membrane / negative regulation of blood vessel endothelial cell migration / fibronectin binding / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / negative regulation of cell cycle / epithelial to mesenchymal transition / positive regulation of collagen biosynthetic process / ECM proteoglycans / positive regulation of blood vessel endothelial cell migration / Integrin cell surface interactions / vasculogenesis / voltage-gated calcium channel activity / lymph node development / chondrocyte differentiation / hematopoietic progenitor cell differentiation 類似検索 - 分子機能 | ||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Sus scrofa (ブタ) | ||||||||||||||||||||||||
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 | ||||||||||||||||||||||||
データ登録者 | Campbell MG / Cormier A | ||||||||||||||||||||||||
資金援助 | 米国, 7件
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引用 | ジャーナル: Cell / 年: 2020 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 |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_20794.map.gz | 1.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-20794-v30.xml emd-20794.xml | 21.5 KB 21.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_20794.png | 99.6 KB | ||
Filedesc metadata | emd-20794.cif.gz | 7.4 KB | ||
その他 | emd_20794_additional.map.gz | 52.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20794 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20794 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_20794_validation.pdf.gz | 319.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_20794_full_validation.pdf.gz | 319.3 KB | 表示 | |
XML形式データ | emd_20794_validation.xml.gz | 6.5 KB | 表示 | |
CIF形式データ | emd_20794_validation.cif.gz | 7.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20794 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20794 | 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 (文献) 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 | EMPIAR-10343 (タイトル: CryoEM dataset containing multiple conformations of the asymmetric αVβ8 integrin bound to latent TGF-β on a holey carbon grid (strongly preferred orientations) 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]) EMPIAR-10344 (タイトル: CryoEM dataset containing multiple conformations of the asymmetric αVβ8 integrin bound to latent TGF-β on a graphene oxide grid (preferred orientations) 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]) |
-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_20794.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
-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: Homo sapiens (ヒト) |
-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: Sus scrofa (ブタ) |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 112.813352 KDa |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
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: Homo sapiens (ヒト) |
分子量 | 理論値: 81.276664 KDa |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
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: Sus scrofa (ブタ) |
分子量 | 理論値: 41.434449 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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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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: 7.5 |
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グリッド | 材質: GRAPHENE OXIDE |
凍結 | 凍結剤: ETHANE |
-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: FIELD EMISSION GUN |
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 |
-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 |