- EMDB-23048: Cryo-EM structure of human Factor V at 3.3 Angstrom resolution -
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基本情報
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データベース: EMDB / ID: EMD-23048
タイトル
Cryo-EM structure of human Factor V at 3.3 Angstrom resolution
マップデータ
試料
複合体: human Factor V
タンパク質・ペプチド: Coagulation factor V
機能・相同性
機能・相同性情報
response to vitamin K / platelet alpha granule / Cargo concentration in the ER / blood circulation / COPII-mediated vesicle transport / COPII-coated ER to Golgi transport vesicle / Common Pathway of Fibrin Clot Formation / endoplasmic reticulum-Golgi intermediate compartment membrane / platelet alpha granule lumen / Post-translational protein phosphorylation ...response to vitamin K / platelet alpha granule / Cargo concentration in the ER / blood circulation / COPII-mediated vesicle transport / COPII-coated ER to Golgi transport vesicle / Common Pathway of Fibrin Clot Formation / endoplasmic reticulum-Golgi intermediate compartment membrane / platelet alpha granule lumen / Post-translational protein phosphorylation / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / blood coagulation / extracellular vesicle / Platelet degranulation / copper ion binding / endoplasmic reticulum lumen / extracellular space / extracellular region / membrane / plasma membrane 類似検索 - 分子機能
Coagulation factor 5/8-like / : / Coagulation factors 5/8 type C domain (FA58C) signature 2. / Multicopper oxidases, conserved site / Multicopper oxidases signature 1. / Coagulation factors 5/8 type C domain (FA58C) signature 1. / Coagulation factor 5/8 C-terminal domain, discoidin domain / Coagulation factors 5/8 type C domain (FA58C) profile. / F5/8 type C domain / Coagulation factor 5/8 C-terminal domain ...Coagulation factor 5/8-like / : / Coagulation factors 5/8 type C domain (FA58C) signature 2. / Multicopper oxidases, conserved site / Multicopper oxidases signature 1. / Coagulation factors 5/8 type C domain (FA58C) signature 1. / Coagulation factor 5/8 C-terminal domain, discoidin domain / Coagulation factors 5/8 type C domain (FA58C) profile. / F5/8 type C domain / Coagulation factor 5/8 C-terminal domain / Multicopper oxidase, N-terminal / Multicopper oxidase / Cupredoxin / Galactose-binding-like domain superfamily 類似検索 - ドメイン・相同性
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
米国
引用
ジャーナル: Blood / 年: 2021 タイトル: Cryo-EM structures of human coagulation factors V and Va. 著者: Eliza A Ruben / Michael J Rau / James A J Fitzpatrick / Enrico Di Cera / 要旨: Coagulation factor V (fV) is the precursor of fVa, which, together with fXa, Ca2+, and phospholipids, defines the prothrombinase complex and activates prothrombin in the penultimate step of the ...Coagulation factor V (fV) is the precursor of fVa, which, together with fXa, Ca2+, and phospholipids, defines the prothrombinase complex and activates prothrombin in the penultimate step of the coagulation cascade. We solved the cryogenic electron microscopy (cryo-EM) structures of human fV and fVa at atomic (3.3 Å) and near-atomic (4.4 Å) resolution, respectively. The structure of fV reveals the entire A1-A2-B-A3-C1-C2 assembly, but with a surprisingly disordered B domain. The C1 and C2 domains provide a platform for interaction with phospholipid membranes and support the A1 and A3 domains, with the A2 domain sitting on top of them. The B domain is highly dynamic and visible only for short segments connecting to the A2 and A3 domains. The A2 domain reveals all sites of proteolytic processing by thrombin and activated protein C, a partially buried epitope for binding fXa, and fully exposed epitopes for binding activated protein C and prothrombin. Removal of the B domain and activation to fVa exposes the sites of cleavage by activated protein C at R306 and R506 and produces increased disorder in the A1-A2-A3-C1-C2 assembly, especially in the C-terminal acidic portion of the A2 domain that is responsible for prothrombin binding. Ordering of this region and full exposure of the fXa epitope emerge as necessary steps in the assembly of the prothrombin-prothrombinase complex. These structures offer molecular context for the function of fV and fVa and pioneer the analysis of coagulation factors by cryo-EM.