+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-20796 | ||||||||||||||||||||||||
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タイトル | Integrin alpha-v beta-8 in complex with Fabs C6-RGD3 and 11D12v2 (Primary map: sharpened, focused refinement. Five additional maps.) | ||||||||||||||||||||||||
マップデータ | Integrin alpha-v beta-8 in complex with Fabs C6-RGD3 and 11D12v2 (Primary map: sharpened, focused refinement, 3.6 A resolution. Five additional maps.) | ||||||||||||||||||||||||
試料 |
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キーワード | glycoprotein / adhesion / signaling / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 ganglioside metabolic process / Langerhans cell differentiation / integrin alphav-beta8 complex / integrin alphav-beta6 complex / hard palate development / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / opsonin binding / integrin alphav-beta1 complex ...ganglioside metabolic process / Langerhans cell differentiation / integrin alphav-beta8 complex / integrin alphav-beta6 complex / hard palate development / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / opsonin binding / integrin alphav-beta1 complex / Cross-presentation of particulate exogenous antigens (phagosomes) / extracellular matrix protein binding / Laminin interactions / placenta blood vessel development / negative regulation of lipoprotein metabolic process / integrin alphav-beta3 complex / negative regulation of low-density lipoprotein receptor activity / alphav-beta3 integrin-PKCalpha complex / alphav-beta3 integrin-HMGB1 complex / regulation of phagocytosis / negative regulation of lipid transport / Elastic fibre formation / alphav-beta3 integrin-IGF-1-IGF1R complex / 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 / apolipoprotein A-I-mediated signaling pathway / apoptotic cell clearance / wound healing, spreading of epidermal cells / cartilage development / positive regulation of intracellular signal transduction / heterotypic cell-cell adhesion / integrin complex / Molecules associated with elastic fibres / microvillus membrane / cell adhesion mediated by integrin / negative chemotaxis / Syndecan interactions / cell-substrate adhesion / endodermal cell differentiation / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / PECAM1 interactions / lamellipodium membrane / fibronectin binding / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / ECM proteoglycans / voltage-gated calcium channel activity / Integrin cell surface interactions / vasculogenesis / specific granule membrane / phagocytic vesicle / coreceptor activity / extrinsic apoptotic signaling pathway in absence of ligand / ERK1 and ERK2 cascade / positive regulation of cell adhesion / cell-matrix adhesion / substrate adhesion-dependent cell spreading / transforming growth factor beta receptor signaling pathway / Signal transduction by L1 / integrin-mediated signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / calcium ion transmembrane transport / protein kinase C binding / response to virus / VEGFA-VEGFR2 Pathway / cell-cell adhesion / ruffle membrane / positive regulation of angiogenesis / cell migration / integrin binding / virus receptor activity / positive regulation of cytosolic calcium ion concentration / protease binding / angiogenesis / cell adhesion / positive regulation of cell migration / immune response / symbiont entry into host cell / external side of plasma membrane / negative regulation of gene expression / focal adhesion / positive regulation of cell population proliferation / Neutrophil degranulation / positive regulation of gene expression / cell surface / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / 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: 3.56 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_20796.map.gz | 775.2 KB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-20796-v30.xml emd-20796.xml | 31.3 KB 31.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_20796.png | 91.4 KB | ||
Filedesc metadata | emd-20796.cif.gz | 7.6 KB | ||
その他 | emd_20796_additional_1.map.gz emd_20796_additional_2.map.gz emd_20796_additional_3.map.gz emd_20796_additional_4.map.gz emd_20796_additional_5.map.gz | 775.2 KB 1.3 MB 51.9 MB 2.3 MB 51.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20796 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20796 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_20796_validation.pdf.gz | 318.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_20796_full_validation.pdf.gz | 317.8 KB | 表示 | |
XML形式データ | emd_20796_validation.xml.gz | 6.4 KB | 表示 | |
CIF形式データ | emd_20796_validation.cif.gz | 7.3 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20796 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20796 | 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_20796.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 Fabs C6-RGD3 and 11D12v2 (Primary map: sharpened, focused refinement, 3.6 A resolution. Five additional maps.) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 Fabs C6-RGD3...
ファイル | emd_20796_additional_1.map | ||||||||||||
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注釈 | Integrin alpha-v beta-8 in complex with Fabs C6-RGD3 and 11D12v2 (Additional map: unsharpened, focused refinement.) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Integrin alpha-v beta-8 in complex with Fabs C6-RGD3...
ファイル | emd_20796_additional_2.map | ||||||||||||
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注釈 | Integrin alpha-v beta-8 in complex with Fabs C6-RGD3 and 11D12v2 (Additional map: sharpened, focused refinement ii, 3.9 A resolution) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Integrin alpha-v beta-8 in complex with Fabs C6-RGD3...
ファイル | emd_20796_additional_3.map | ||||||||||||
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注釈 | Integrin alpha-v beta-8 in complex with Fabs C6-RGD3 and 11D12v2 (Additional map: unsharpened, focused refinement ii.) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Integrin alpha-v beta-8 in complex with Fabs C6-RGD3...
ファイル | emd_20796_additional_4.map | ||||||||||||
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注釈 | Integrin alpha-v beta-8 in complex with Fabs C6-RGD3 and 11D12v2 (Additional map: sharpened, full complex, 4.1 A resolution) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Integrin alpha-v beta-8 in complex with Fabs C6-RGD3...
ファイル | emd_20796_additional_5.map | ||||||||||||
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注釈 | Integrin alpha-v beta-8 in complex with Fabs C6-RGD3 and 11D12v2 (Additional map: unsharpened, full complex.) | ||||||||||||
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 : Ternary complex of Integrin alpha-v beta-8 with Fab C6-RGD3 and F...
+超分子 #1: Ternary complex of Integrin alpha-v beta-8 with Fab C6-RGD3 and F...
+超分子 #2: alpha-v beta-8 integrin
+超分子 #3: C6-RGD3 Fab
+超分子 #4: 11D12v2 Fab
+分子 #1: Integrin alpha-V
+分子 #2: Integrin beta-8
+分子 #3: C6-RGD3 heavy chain Fab
+分子 #4: C6-RGD3 light chain Fab
+分子 #7: CALCIUM ION
+分子 #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #9: MAGNESIUM ION
-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 | 詳細: unspecified |
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) 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: 3.56 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 221159 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |