Interactions of Fibrinogen Gamma' Variant with Thrombin

描述(申请人提供)：我的长期目标是确定纤维蛋白原的伽马变异形式和凝血酶之间的相互作用。这项建议的具体目的是： 将钙离子结合位点(S)定位在伽马链上。要检验的假设是，伽马链在纤维蛋白原中提供了一个额外的钙结合部位(S)。II-确定伽马链对凝血酶对蛋白质底物的酶活性的影响。需要检验的假设是，伽马链通过与Exosite II结合来调节底物的凝血酶裂解。 确定伽马链对蛋白酶抑制物抑制凝血酶的影响。需要检验的假设是，伽马链的纤溶酶裂解产物催化肝素依赖的抑制物对凝血酶的抑制，并且伽马链与肝素依赖的抑制物结合。 确定伽玛链对凝血酶的促凝活性和全血浆中的血小板聚集活性的影响。需要检验的假设是，伽马链的纤溶酶裂解产物在血浆中起到抗凝剂的作用。

DESCRIPTION (provided by applicant): My long-term goals are to define the interactions between the gamma variant form of fibrinogen and thrombin. The specific aims of this proposal are to: I- Map the Ca2+ binding site(s) on the gamma chain. The hypothesis to be tested is that the gamma chain provides an additional Ca2+ binding site(s) in fbrinogen.II - Determine the effect of the gamma chain on thrombin's enzymatic activity towards protein substrates. The hypothesis to be tested is that the gamma chain modulates thrombin cleavage of substrates by binding to exosite II. III- Determine the effect of the gamma chain on thrombin inhibition by protease inhibitors. The hypothesis to be tested is that a plasmin cleavage product of the gamma chain catalyzes thrombin inhibition by heparin-dependent inhibitors, and that the gamma chain binds to heparin-dependent inhibitors. IV- Determine the effect of the gamma chain on thrombin's procoagulant activity and platelet aggregating activity in whole plasma. The hypothesis to be tested is that a plasmin cleavage product of the gamma chain acts as an anticoagulant in plasma.