Bos Mettine H A, Camire Rodney M
Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia.
J Coagul Disord. 2010 Jul 1;2(2):19-27.
A hallmark of hemostasis is that cells and proteins involved in the formation of a blood clot remain in a quiescent state and are only activated following an appropriate stimulus. The homologous proteins factors V and VIII cannot participate to any significant degree in their macromolecular enzyme complexes and are thus considered procofactors. Activity is generated following limited proteolysis, indicating that the conversion of the procofactors to factor Va and factor VIIIa must result in structural changes that impart cofactor function. The proteolytic events that lead to the activation of these proteins have been extensively characterized over the past three decades. However, a fundamental understanding of the mechanism(s) by which these proteins are kept as inactive procofactors and how specific bond cleavage facilitates the conversion to the active cofactor state is only starting to become known. These molecular processes undoubtedly play critical regulatory roles, evolved to maintain normal hemostasis since factor Va and factor VIIIa have a tremendous influence on thrombin generation. This review will detail our current understanding of the molecular process of procofactor activation and highlight structural features that play a major role in factor V and factor VIII activation.
止血的一个标志是参与血凝块形成的细胞和蛋白质处于静止状态，仅在适当刺激后才被激活。同源蛋白因子V和因子VIII在其大分子酶复合物中不能显著参与，因此被视为前辅因子。有限的蛋白水解后产生活性，这表明前辅因子转化为因子Va和因子VIIIa必然导致赋予辅因子功能的结构变化。在过去三十年中，导致这些蛋白质激活的蛋白水解事件已得到广泛表征。然而，对于这些蛋白质如何作为无活性前辅因子保持以及特定的键断裂如何促进向活性辅因子状态转化的机制的基本理解才刚刚开始为人所知。这些分子过程无疑起着关键的调节作用，由于因子Va和因子VIIIa对凝血酶生成有巨大影响，它们的进化是为了维持正常止血。本综述将详细阐述我们目前对前辅因子激活分子过程的理解，并突出在因子V和因子VIII激活中起主要作用的结构特征。
