9TLE

Structure of human prothrombinase with prothrombin

9TLE の概要

• エントリーDOI: 10.2210/pdb9tle/pdb
• 関連するPDBエントリー: 9I2H
• EMDBエントリー: 56052
• 分子名称: Activated factor Xa heavy chain, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (12 entities in total)
• 機能のキーワード: prothrombinase, factor va, factor xa, prothrombin, blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 270478.79

構造登録者

Faille, A.,Ustok, F.I.,Warren, A.,Huntingon, J.A. (登録日: 2025-12-10, 公開日: 2026-08-12)

主引用文献

Ustok, F.I.,Faille, A.,Warren, A.J.,Huntington, J.A.
Prothrombinase processivity is conferred by substrate allostery.
Embo J., 45:3954-3977, 2026

PubMed Abstract: The prothrombinase complex, comprised of factor (f) Xa and fVa, converts prothrombin to thrombin through sequential cleavage at two sites in a rapid and processive manner. The molecular basis of prothrombin processing is an enzymatical mystery that to solve requires structural insight into how the substrate and intermediate bind to prothrombinase. Here we present two 3.1 Å cryo-EM structures of prothrombinase bound to prothrombin and to meizothrombin. The prothrombin complex revealed a surprising interaction between the end of the heavy chain of fVa with exosite I of prothrombin, accounting for 70% of the contact interface. Triggering of the zymogen-to-protease conformational change following cleavage at Arg320 alters all domain-domain and fVa interactions observed for prothrombin, and results in a large-scale rearrangement of meizothrombin that presents the second cleavage site (Arg271) for processing. Together, these structures reveal a remarkable enzymatic mechanism that requires the active participation of the substrate itself, and introduces a new paradigm of 'substrate allostery'.

PubMed: 42020574
DOI: 10.1038/s44318-026-00782-4

実験手法

ELECTRON MICROSCOPY (3.1 Å)