多尺度分子模拟研究来自于无类囊体蓝藻的五聚体门控离子通道门控机理  

Multi-scale Molecular Simulations Study on the Gating Mechanism in a Pentameric Ligand-gated Ion Channel from Gloebacter Violaceus

作　　者：于辉[1] 李卓[1] 赵熹[1] 黄旭日[1] 

机构地区：[1]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130061

出　　处：《化学学报》2011年第14期1639-1644,共6页Acta Chimica Sinica

摘　　要：五聚体门控离子通道是一个重要膜蛋白家族,在生理学过程中起到重要作用.我们以来自无类囊体蓝藻(Gloebacter violaceus:GLIC)的五聚体门控离子通道X-ray结构为模型,进行总共1.05μs的粗粒化分子模拟,并结合原子级分子模拟方法,观察到其离子通道的闭合和相应的四级结构扭转.我们发现其位于跨膜区组成通道的M2螺旋通过倾斜-旋转(指向通道中心)的协调运动来完成通道闭合.进一步分析并结合前人的实验结果,我们提出了该离子通道门控过程的可能的"连锁反应"机理:由单独亚基的M2螺旋前部构象变化引发,使该亚基发生整体的构象变化,并且将这种变化传递到了邻近的亚基,进而带动整个通道的构象变化,最终完成通道的闭合.Pentameric ligand-gated ion channels belong to an important family of membrane proteins and play key roles in physiological processes.Based on the X-ray structure of prokaryotic pentameric ligand-gated ion channels from Gloebacter violaceus（GLIC）,we performed a total of 1.05 ？s coarse-grained molecular simulations,combining with atomic-level molecular simulation,and observed the pore closure and corresponding quaternary twist.We found that the pore closure by a concerted motion of rotating-tilting（toward the pore） of helices M2.Combining with previous experimental results,a model of describing the conformational transition for channel gating process is derived from our simulations： the top of the M2 helix occurs large conformational fluctuations,followed by a global conformational changes of the whole subunit;this process passes from one subunit to the neighbor one,finally,leading to the entire channel conforma-tional changes,such as a ＂chain-reaction＂.

关 键 词：五聚体门控离子通道 门控 粗粒化 

分 类 号：Q945[生物学—植物学]