Activation of Tissue Factor by a Disulphide-Bond Switch

该项目将定义组织因子激活的分子机制，血液凝固的引发剂，并设计和测试阻断这种激活的新型抗体疗法。申请人认为组织因子是由二硫键开关激活的。如果这一假设被证明是正确的，这将是通过这种方式激活哺乳动物蛋白质的第一个例子，而且，由于激活发生在血管内的膜表面上，因此非常适合于治疗干预。组织因子激活和血栓形成是急性心肌梗死、不稳定型心绞痛和缺血性卒中的促发事件，这些事件是澳大利亚大多数死亡的原因。

This project will define the molecular mechanism of activation of tissue factor, the initiator of blood coagulation, and design and test novel antibody therapeutics that block this activation. The applicant suggests that tissue factor is activated by a disulphide-bond switch. Should this hypothesis prove correct it would be the first example of activation of a mammalian protein by this means and, moreover, would be very amenable to therapeutic intervention because activation occurs on the membrane surface inside blood vessels. Tissue factor activation and thrombus formation is the precipitating event in acute myocardial infarction, unstable angina and ischemic stroke, which are responsible for the majority of deaths in Australia.