8FDG

Cryo-EM structure of coagulation factor V short

8FDG の概要

• エントリーDOI: 10.2210/pdb8fdg/pdb
• EMDBエントリー: 29008 29009 29010 29011
• 分子名称: Coagulation factor V (1 entity in total)
• 機能のキーワード: blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 172748.23

構造登録者

Mohammed, B.M.,Pelc, L.A.,Rau, M.J.,Di Cera, E. (登録日: 2022-12-03, 公開日: 2023-03-15, 最終更新日: 2024-10-16)

主引用文献

Mohammed, B.M.,Pelc, L.A.,Rau, M.J.,Di Cera, E.
Cryo-EM structure of coagulation factor V short.
Blood, 141:3215-3225, 2023

PubMed Abstract: Coagulation factor V (fV) is the precursor of activated fV (fVa), an essential component of the prothrombinase complex required for the rapid activation of prothrombin in the penultimate step of the coagulation cascade. In addition, fV regulates the tissue factor pathway inhibitor α (TFPIα) and protein C pathways that inhibit the coagulation response. A recent cryogenic electron microscopy (cryo-EM) structure of fV has revealed the architecture of its A1-A2-B-A3-C1-C2 assembly but left the mechanism that keeps fV in its inactive state unresolved because of an intrinsic disorder in the B domain. A splice variant of fV, fV short, carries a large deletion of the B domain that produces constitutive fVa-like activity and unmasks epitopes for the binding of TFPIα. The cryo-EM structure of fV short was solved at 3.2 Å resolution and revealed the arrangement of the entire A1-A2-B-A3-C1-C2 assembly. The shorter B domain stretches across the entire width of the protein, making contacts with the A1, A2, and A3 domains but suspended over the C1 and C2 domains. In the portion distal to the splice site, several hydrophobic clusters and acidic residues provide a potential binding site for the basic C-terminal end of TFPIα. In fV, these epitopes may bind intramolecularly to the basic region of the B domain. The cryo-EM structure reported in this study advances our understanding of the mechanism that keeps fV in its inactive state, provides new targets for mutagenesis and facilitates future structural analysis of fV short in complex with TFPIα, protein S, and fXa.

PubMed: 36862974
DOI: 10.1182/blood.2022019486

実験手法

ELECTRON MICROSCOPY (3.2 Å)