恢复蛋白EF-hand与钙离子去耦合作用的拉伸分子动力学模拟  

Decoupling Interactions between EF-hands of Recoverin and Ca^(2+):Steered Molecular Dynamics Simulation

作　　者：李吉来[1,2] 耿彩云[2] 步宇翔[1] 张亮[1] 张来斌[1] 黄旭日[2] 孙家锺[2] 

机构地区：[1]山东大学化学与化工学院胶体与界面化学教育部重点实验室,济南250100 [2]吉林大学理论化学研究所理论化学计算国家重点实验室,长春130023

出　　处：《化学学报》2009年第14期1597-1602,共6页Acta Chimica Sinica

基　　金：国家自然科学基金(No.20773048);山东省博士后创新(No.200702019);中国博士后科学基金(No.20070421075)资助项目

摘　　要：恢复蛋白Recoverin是一重要的神经钙传感蛋白.为澄清EF-hand与Ca2+耦合/去耦合作用机制,采用拉伸分子动力学(SMD)方法对其进行了一系列等外力和等速度的非平衡分子动力学模拟.研究结果表明EF-2和EF-3loop区氨基酸螯合Ca2+能力大小顺序分别为Asn-76<Thr-80<Glu-85<Asp-74<Asp-78和Thr-116<Glu-121<Asp-110<Asn-114<Asp-112.结构域EF-3比EF-2耦合Ca2+离子的能力强.EF-handloop环中的Asp-78和Asp-112残基在该信号传导过程中起至关重要的作用.基于理论模拟和试验结果我们推测Ca2+离子诱导恢复蛋白的构象转变是一个两步过程.在该细胞信号Ca2+离子与恢复蛋白耦合过程中,EF-3和Ca2+耦合作用触发恢复蛋白构象转变,而EF-2和Ca2+的耦合作用起续航作用,促使变构过程完成.Recoverin is an important branch of neuronal calcium sensor. To clarify the coupling/decoupling interaction mechanism between EF-hands and Ca^2＋, a series of constant force pulling and constant velocity pulling non-equilibrium molecular dynamics simulations were performed by using a steered molecular dynamics method. The results show that, among the residues in the EF-2 and EF-3 loop motifs, the orders of chelation abilities are Asn-76〈Thr-80〈Glu-85〈Asp-74〈Asp-78 and Thr-116〈Glu-121〈Asp-110〈 Asn-114〈Asp-112, respectively. The coupling interaction between EF-3 and Ca^2＋ is more powerful than that between EF-2 and Ca^2＋. The residues of Asp-78 and Asp-112 in the EF-hand loops play vital roles in the conformational transition involving signal transduction. According to the theoretical simulation and experimental results, it is safe to make the conclusion that the Ca^2＋-recoverin allostery is a two-step process. In the cell signal process of Ca^2＋ coupling with recoverin, the interaction of Ca^2＋ with EF-3 triggers the conformational transition of recoverin, whereas it is carried transition completely,whereas it is carried over by Ca^2＋ interacting with EF-2, which makes the transition completely.

关 键 词：恢复蛋白 变构过程 信号传导 去耦合作用 拉伸分子动力学 Ca^2+/豆蔻酰基开关 

分 类 号：Q51[生物学—生物化学]