+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-42405 | |||||||||||||||||||||||||||
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タイトル | Preliminary map of the Prothrombin-prothrombinase complex on nano discs | |||||||||||||||||||||||||||
マップデータ | Unsharpened map | |||||||||||||||||||||||||||
試料 |
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キーワード | Coagulation / Prothrombin / Prothrombinase / nanodisc / complex / BLOOD CLOTTING | |||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 response to vitamin K / coagulation factor Xa / platelet alpha granule / Cargo concentration in the ER / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / blood circulation / Extrinsic Pathway of Fibrin Clot Formation / COPII-mediated vesicle transport ...response to vitamin K / coagulation factor Xa / platelet alpha granule / Cargo concentration in the ER / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / blood circulation / Extrinsic Pathway of Fibrin Clot Formation / COPII-mediated vesicle transport / positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / COPII-coated ER to Golgi transport vesicle / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of astrocyte differentiation / negative regulation of platelet activation / positive regulation of collagen biosynthetic process / positive regulation of TOR signaling / negative regulation of cytokine production involved in inflammatory response / positive regulation of blood coagulation / negative regulation of fibrinolysis / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / fibrinolysis / regulation of cytosolic calcium ion concentration / Intrinsic Pathway of Fibrin Clot Formation / endoplasmic reticulum-Golgi intermediate compartment membrane / Peptide ligand-binding receptors / positive regulation of release of sequestered calcium ion into cytosol / platelet alpha granule lumen / acute-phase response / Regulation of Complement cascade / negative regulation of proteolysis / Cell surface interactions at the vascular wall / lipopolysaccharide binding / Post-translational protein phosphorylation / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / positive regulation of insulin secretion / phospholipid binding / platelet activation / response to wounding / positive regulation of protein localization to nucleus / Golgi lumen / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / antimicrobial humoral immune response mediated by antimicrobial peptide / positive regulation of reactive oxygen species metabolic process / blood coagulation / extracellular vesicle / Thrombin signalling through proteinase activated receptors (PARs) / Platelet degranulation / signaling receptor activity / heparin binding / regulation of cell shape / positive regulation of cell growth / G alpha (q) signalling events / collagen-containing extracellular matrix / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / blood microparticle / cell surface receptor signaling pathway / positive regulation of cell migration / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / copper ion binding / endoplasmic reticulum lumen / external side of plasma membrane / serine-type endopeptidase activity / signaling receptor binding / calcium ion binding / positive regulation of cell population proliferation / proteolysis / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) | |||||||||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 6.47 Å | |||||||||||||||||||||||||||
データ登録者 | Stojanovski BM / Mohammed BM / Di Cera E | |||||||||||||||||||||||||||
資金援助 | 米国, 8件
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引用 | ジャーナル: Subcell Biochem / 年: 2024 タイトル: The Prothrombin-Prothrombinase Interaction. 著者: Bosko M Stojanovski / Bassem M Mohammed / Enrico Di Cera / 要旨: The hemostatic response to vascular injury entails a sequence of proteolytic events where several inactive zymogens of the trypsin family are converted to active proteases. The cascade starts with ...The hemostatic response to vascular injury entails a sequence of proteolytic events where several inactive zymogens of the trypsin family are converted to active proteases. The cascade starts with exposure of tissue factor from the damaged endothelium and culminates with conversion of prothrombin to thrombin in a reaction catalyzed by the prothrombinase complex composed of the enzyme factor Xa, cofactor Va, Ca, and phospholipids. This cofactor-dependent activation is paradigmatic of analogous reactions of the blood coagulation and complement cascades, which makes elucidation of its molecular mechanism of broad significance to the large class of trypsin-like zymogens to which prothrombin belongs. Because of its relevance as the most important reaction in the physiological response to vascular injury, as well as the main trigger of pathological thrombotic complications, the mechanism of prothrombin activation has been studied extensively. However, a molecular interpretation of this mechanism has become available only recently from important developments in structural biology. Here we review current knowledge on the prothrombin-prothrombinase interaction and outline future directions for the study of this key reaction of the coagulation cascade. | |||||||||||||||||||||||||||
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_42405.map.gz | 253.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-42405-v30.xml emd-42405.xml | 22.3 KB 22.3 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_42405_fsc.xml | 16.9 KB | 表示 | FSCデータファイル |
画像 | emd_42405.png | 109.7 KB | ||
マスクデータ | emd_42405_msk_1.map | 512 MB | マスクマップ | |
Filedesc metadata | emd-42405.cif.gz | 5 KB | ||
その他 | emd_42405_additional_1.map.gz emd_42405_additional_2.map.gz emd_42405_half_map_1.map.gz emd_42405_half_map_2.map.gz | 474.3 MB 474.3 MB 474.8 MB 474.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-42405 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42405 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_42405_validation.pdf.gz | 885.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_42405_full_validation.pdf.gz | 884.7 KB | 表示 | |
XML形式データ | emd_42405_validation.xml.gz | 26.5 KB | 表示 | |
CIF形式データ | emd_42405_validation.cif.gz | 35.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42405 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42405 | HTTPS FTP |
-関連構造データ
関連構造データ | 9cthMC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_42405.map.gz / 形式: CCP4 / 大きさ: 512 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Unsharpened map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.94 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_42405_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 |
-追加マップ: original half-map A
ファイル | emd_42405_additional_1.map | ||||||||||||
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注釈 | original half-map A | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: original half-map B
ファイル | emd_42405_additional_2.map | ||||||||||||
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注釈 | original half-map B | ||||||||||||
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 B filtered to resolution (6.5A)
ファイル | emd_42405_half_map_1.map | ||||||||||||
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注釈 | half map B filtered to resolution (6.5A) | ||||||||||||
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 A filtered to resolution (6.5A)
ファイル | emd_42405_half_map_2.map | ||||||||||||
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注釈 | half map A filtered to resolution (6.5A) | ||||||||||||
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 : Prothrombin_Prothrombinase complex on lipid nanodiscs.
全体 | 名称: Prothrombin_Prothrombinase complex on lipid nanodiscs. |
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要素 |
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-超分子 #1: Prothrombin_Prothrombinase complex on lipid nanodiscs.
超分子 | 名称: Prothrombin_Prothrombinase complex on lipid nanodiscs. タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 詳細: The complex is made of coagulation factor Va (derived from human plasma), coagulation factor Xa (Recombinantly expressed in BHK cells) and Prothrombin (Recombinantly expressed in BHK cells). ...詳細: The complex is made of coagulation factor Va (derived from human plasma), coagulation factor Xa (Recombinantly expressed in BHK cells) and Prothrombin (Recombinantly expressed in BHK cells). The nanodisc component of the complex is made of the scaffold protein MSP1E3D1 (Recombinantly expressed in bacteria) and the phospholipid component was Porcine Brain phosphatidylserine. |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 組織: Blood |
-超分子 #2: Coagulation Factor Va
超分子 | 名称: Coagulation Factor Va / タイプ: organelle_or_cellular_component / ID: 2 / 親要素: 1 |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 組織: Blood |
-超分子 #3: Coagulation Factor Xa
超分子 | 名称: Coagulation Factor Xa / タイプ: organelle_or_cellular_component / ID: 3 / 親要素: 1 詳細: Catalytically inactive full length mutant S379A with C-terminus HPC4 tag. |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 組織: Blood |
-超分子 #4: Prothrombin
超分子 | 名称: Prothrombin / タイプ: organelle_or_cellular_component / ID: 4 / 親要素: 1 詳細: Catalytically inactive full length mutant S525A with C-terminus HPC4 tag |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 組織: Blood |
-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
濃度 | 0.01 mg/mL |
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緩衝液 | pH: 7.4 / 詳細: 20 mM HEPES, 150 mM NaCl, and 5 mM CaCl2 |
グリッド | 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV |
詳細 | Prothrombin:FVa:FXa were mixed in 2:1:2 ratio. 0.01 mg/mL total protein was used for freezing. |
-電子顕微鏡法
顕微鏡 | TFS GLACIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 実像数: 2390 / 平均電子線量: 51.28 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 50.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.4 µm / 最小 デフォーカス(公称値): 0.8 µm |
試料ステージ | ホルダー冷却材: NITROGEN |
+画像解析
-原子モデル構築 1
精密化 | プロトコル: AB INITIO MODEL |
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得られたモデル | PDB-9cth: |