8TY1

Cryo-EM structure of coagulation factor VIII bound to NB2E9

8TY1 の概要

• エントリーDOI: 10.2210/pdb8ty1/pdb
• EMDBエントリー: 41710
• 分子名称: Coagulation factor VIII, NB2E9 light chain, NB2E9 heavy chain, ... (4 entities in total)
• 機能のキーワード: coagulation, inhibitor antibody, factor viii, blood clotting-inhibitor complex, blood clotting/inhibitor
• 由来する生物種: Sus scrofa (pig); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 219419.54

構造登録者

Childers, K.C.,Spiegel, P.C. (登録日: 2023-08-24, 公開日: 2023-09-13, 最終更新日: 2025-06-04)

主引用文献

Childers, K.C.,Cowper, B.,Vaughan, J.D.,McGill, J.R.,Davulcu, O.,Lollar, P.,Doering, C.B.,Coxon, C.H.,Spiegel Jr., P.C.
Structural basis for inhibition of coagulation factor VIII reveals a shared antigenic hotspot on the C1 domain.
J.Thromb.Haemost., 22:2449-2459, 2024

PubMed Abstract: Hemophilia A arises from dysfunctional or deficient coagulation factor (F)VIII and leads to inefficient fibrin clot formation and uncontrolled bleeding events. The development of antibody inhibitors is a clinical complication in hemophilia A patients receiving FVIII replacement therapy. LE2E9 is an anti-C1 domain inhibitor previously isolated from a mild/moderate hemophilia A patient and disrupts FVIII interactions with von Willebrand factor and FIXa, though the intermolecular contacts that underpin LE2E9-mediated FVIII neutralization are undefined.

PubMed: 38849084
DOI: 10.1016/j.jtha.2024.05.024

実験手法

ELECTRON MICROSCOPY (3.46 Å)