EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryo-EM.
ジャーナル・号・ページ	J Thromb Haemost, Year 2026
掲載日	2026年8月21日
著者	Bassem M Mohammed / Samantha Deavila / Tristan Friet / Isabella Dattilio /
PubMed 要旨	BACKGROUND: Factor XI (FXI) occupies a unique and clinically significant niche, bridging the tissue factor-driven and contact-driven coagulation pathways. Irrespective of the trigger, activated ...BACKGROUND: Factor XI (FXI) occupies a unique and clinically significant niche, bridging the tissue factor-driven and contact-driven coagulation pathways. Irrespective of the trigger, activated factor XI (FXIa) contributes to clotting by activating factor IX (FIX). Biochemical studies established that this reaction requires the membrane-binding FIX-Gla domain to engage an exosite on the FXIa Apple 3 (A3) domain, that only become available upon FXI activation. Structural data for FXIa, FIX, FIXaβ, and the FXIa:FIX complex are lacking; current understanding relies on zymogen FXI crystal structures and homology modeling of FXIa after kallikrein. OBJECTIVES: Elucidate the high-resolution structure of FXIa in functionally relevant conformation in complex with FIX. 手法: We utilized cryogenic electron microscopy (cryo-EM) to determine the structures of human FXIa in complex with its full-length substrate, FIX, and activated product, FIXaβ. RESULTS: We report the first cryo-EM structures of FXIa in complex with its substrate, FIX, and activated FIX (FIXaβ). The structures capture a functionally relevant conformational change in the FXIa catalytic domain and reveals the first view of the entire FIX and FIXaβ. Critically, we visualize the FIX-Gla domain precisely docked to the FXIa-A3 exosite on both subunits of the FXIa dimer. We also define the first step of proteolysis, visualizing the FIX Arg145 inserted into the primary specificity pocket of FXIa. CONCLUSIONS: The structures define the full FXIa:FIX interface providing a structural template for understanding the sequential activation of FIX and for developing a new class of selective allosteric antithrombotic agents.
リンク	J Thromb Haemost / PubMed:42628751
手法	EM (単粒子)
解像度	3.09 - 3.7 Å
構造データ	74584 9zqy EMDB-74584, PDB-9zqy: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.09 Å 74756 9ztk EMDB-74756, PDB-9ztk: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.7 Å 74802 9zub EMDB-74802, PDB-9zub: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.65 Å 74822 9zun EMDB-74822, PDB-9zun: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.55 Å EMDB-74856: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.5 Å EMDB-74858: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.6 Å EMDB-74860: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-74882: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.6 Å EMDB-74883: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-74884: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.4 Å 74894 9zvx EMDB-74894, PDB-9zvx: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-76284: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.44 Å EMDB-76285: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.42 Å EMDB-76286: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.54 Å EMDB-76287: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.54 Å 76288 12bn EMDB-76288, PDB-12bn: Structural insights into the exosite-mediated activation of Factor IX by Factor XIa using cryoEM 手法: EM (単粒子) / 解像度: 3.4 Å
化合物	ChemComp-CA: Unknown entry ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose
由来	homo sapiens (ヒト)
キーワード	BLOOD CLOTTING / Coagulation / Intrinsic Pathway / Complex / Hemophilia / Factor IX / Factor XIa