COORDINATE FUNCTION OF ENZYME COMPLEXES IN HEMOSTASIS

参与凝血的蛋白质必须组装并 功能迅速，以防止创伤后出血。的一个特点 有助于提高效率的凝聚是酶反应的局部化 到膜上。止血过程中的两种膜结合酶 复合体的功能是按顺序产生凝血酶。两种膜 复合体需要蛋白质快速、高亲和力的膜结合 辅因子来定位相应的酶并启动酶功能。 酶复合体在功能上是相关的，因为 第一个复合体是张力酶，它是一种酶，然后与辅因子组装。 形成第二个复合体，凝血酶原酶。虽然它的功能 分离的酶复合体已被表征，没有作用机理 解释这两种酶复合体如何协调工作的信息。 具体地说，任何一种酶复合体对细胞功能的影响 其他未知，以及从Tenase转移Xa因子的机制 凝血酶原酶复合体是未知的。最近，我展示了 两种辅因子蛋白，因子VIII和因子V，增强了 彼此与膜表面的结合。因为因子V和因子 Viii每一种都增强了另一种膜的结合，很可能是它们结合了 为了彼此。因子VIII与因子V的结合可能是物理上的 将两种酶复合体放在一起的机制 为了有效地转移Xa因子形成张力酶复合体 使Va因子形成凝血酶原酶复合体。建议数 实验将检验因子VIII和因子V的机制 快速结合到膜上以及结合的蛋白质在膜上的流动性 薄膜。此外，他们还将表征因子的结合 因子V和确定结合的酶的结果 互动。

The proteins which participate in blood coagulation must assemble and function rapidly in order to prevent bleeding after trauma. A feature of coagulation which aids in efficiency is localization of enzymatic reactions to membranes. In the hemostatic process two membrane-bound enzyme complexes function sequentially to produce thrombin. Both membrane complexes require the rapid, high affinity membrane binding of a protein cofactor to localize the respective enzyme and initiate enzymatic function. The enzyme complexes are functionally related because the product of the first complex, tenase, is an enzyme which then assembles with a cofactor to form the second complex, prothrombinase. Although function of the isolated enzyme complexes has been characterized there is no mechanistic information to explain how the two enzyme complexes function coordinately. Specifically, the effect of either enzyme complex upon the function of the other is unknown and the mechanism of transfer of factor Xa from the tenase complex to the prothrombinase complex is unknown. Recently, I have shown that the two cofactor proteins, factor VIII and factor V, enhance the binding of one another to a membrane surface. Because factor V and factor VIII each enhance membrane binding of the other it is likely that they bind to each other. Binding of factor VIII to factor V may be the physical mechanism which places the two enzyme complexes adjacent to one another in order to efficiently transfer factor Xa to form the tenase enzyme complex to factor Va to form a prothrombinase enzyme complex. The proposed experiments will examine the mechanism whereby factor VIII and factor V bind rapidly to a membrane and the mobility of the bound proteins upon the membrane. In addition they will characterize the binding of factor VIII to factor V and define the enzymatic consequences of the binding interaction.