凝血因子Xa轻链在CaA沸石表面吸附机制的分子动力学模拟研究  

Molecular dynamics study on the adsorption mechanism of coagulation factor Xa light chain on zeolite surfaces

作　　者：何美娟 刘迎春[1] 李嘉辰 王琦[1] Meijuan He;Yingchun Liu;Jiachen Li;Qi Wang(Department of Chemistry,Zhejiang University,Hangzhou 310027,China)

机构地区：[1]浙江大学化学系,杭州310027

出　　处：《中国科学：化学》2023年第9期1770-1780,共11页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:22278351)资助项目。

摘　　要：凝血因子Xa(FXa)和凝血因子Va(FVa)在血小板细胞膜表面可以结合形成凝血酶原酶复合物(FVa–FXa),并可以快速将凝血酶原转化为凝血酶,从而有助于成功止血.研究表明,钙基沸石可以扮演类似无机血小板细胞膜的角色,使得FXa和FVa在其表面自组装并高效催化凝血酶原转化为凝血酶.然而无机沸石表面FXa与FVa在Ca2+作用下的自组装机制并不清楚.鉴于在Ca2+作用下,FXa轻链中羧基谷氨酸(Gla)结构域在细胞膜表面凝血酶原酶复合物自组装中扮演的重要角色,研究FXa轻链在Ca2+作用下在沸石表面的吸附机制具有重要意义.本工作利用分子动力学(MD)模拟研究了Ca2+作用下,FXa轻链分别与磷脂双分子层(PS)细胞膜以及Ca2+交换的LTA型(CaA)沸石表面的相互作用.结果表明,FXa在PS膜表面的吸附主要是Ca2+参与的配位作用,而在CaA沸石表面的吸附主要是带正电的赖氨酸、精氨酸与带负电的沸石骨架之间的静电相互作用,Gla域结合的Ca2+起到稳定结构以及介导蛋白结合到磷脂膜表面的功能.Coagulation factor Xa and coagulation factor Va can bind to form prothrombinase complex at the surface of platelet cell membranes and can rapidly convert prothrombin to thrombin,thus contributing to successful hemostasis.It is shown that calcium-based zeolites can act as inorganic platelet cell membrane,making factor Xa and factor Va selfassemble on its surface and catalyze prothrombin efficiently.However,the self-assembly mechanism of factor Xa and factor Va on the surface of inorganic zeolites under the action of Ca2+is not clear.Given the important role played by the carboxyglutamic acid(Gla)domain in the light chain of factor Xa in the autonomous assembly of the thrombin complex at the cell membrane surface under the action of Ca2+,it is important to study the adsorption mechanism of factor Xa light chain on zeolite surfaces under the action of Ca2.In this work,the interaction of factor Xa light chain with molecular dynamics lipid bilayer membrane and Ca2-exchanged LTA-type zeolite surface was studied by means of molecular dynamics(MD)simulation.The results show that the adsorption of factor Xa on PS membrane is mainly a coordination action of Ca+,and the adsorption on CaA zeolite surfaces is mainly the electrostatic interaction between positively charged lysine,arginine and negatively charged zeolite skeleton,where the Gla domain-bound Ca?*plays a role in stabilizing the structure and mediating protein binding to the surface of the phospholipid membrane.

关 键 词：凝血因子XA 钙基沸石 磷脂膜 静电相互作用 钙离子配位 

分 类 号：TQ424.25[化学工程] R318[医药卫生—生物医学工程]