Kv1.2钾通道闭合的靶向分子动力学模拟  

Targeted molecular dynamics simulation of the closing of Kv1.2 potassium channel

作　　者：钟文宇[1] 郭万林[1] 

机构地区：[1]南京航空航天大学纳米科学研究所,南京210016

出　　处：《计算力学学报》2009年第4期466-470,共5页Chinese Journal of Computational Mechanics

基　　金：国家自然科学基金(10802037;10372044);教育部创新团队(IRT0534);江苏省科技项目前期预研(BK2005217);江苏省自然科学基金创新学者攀登(BK2008042);江苏省博士后资助计划(0802015C)资助项目

摘　　要：钾离子通道是一种能开放或闭合孔道而控制钾离子跨膜流动的膜蛋白。Kv1.2结构是一种开式构型的钾通道结构,也是迄今获得的唯一一种来自真核细胞的钾通道结构。尽管导致Kv1.2结构内螺旋弯曲的PVP序列在KcsA等原核细胞钾通道中不存在,KcsA结构的直式内螺旋闭合构型仍常被作为Kv1.2等真核细胞钾通道的闭式模版。本文在靶向分子动力学模拟中迫使Kv1.2钾通道闭合为KcsA构型,我们发现Kv1.2无法适应KcsA的闭合构型,松弛后内螺旋恢复PVP铰链弯曲,在孔道的腔-门区域形成上下大中间小的沙漏状闭合构型。此构型使开闭构型转换效率更高,可能是钾通道从原核细胞的甘氨酸铰链进化到真核细胞的PXP铰链的原因所在。Potassium channels are membrane proteins which can open or close an ion conducting pore to control the K^＋ flux across the membrane. The Kv1. 2 structure, determined in an open conformation, is the only structure of potassium channels from eukaryotic cells till now. Although the PVP hinge which is bent the inner-helix of Kvl. 2 structure does not exist in KcsA and other prokaryotic potassium channels, the KcsA structure with rigid-body inner-helix was always thought to be the closed template for Kv1. 2 and other eukaryotic potassium channels. Here targeted molecular dynamics simulation is performed, in which Kvl. 2 is forced to close following from the closed conformation of KcsA. We found that Kv1. 2 potassium channel could not match the closed conformation of KcsA because the inner-helix would restore bending at the PVP hinge as the applying force cancelled, while the pore at the cavity-gate region shaped like a sandglass. The conformational transition between the opening and above sandglass like closing could be more effective, which should be the reason why potassium channel evolved to the PXP hinge in eukaryotic cells.

关 键 词：钾通道 门控 蛋白质 分子动力学模拟 Kv1.2 KCSA 

分 类 号：Q66[生物学—生物物理学] Q71