Calcium induced regulation of skeletal troponin--computational insights from molecular dynamics simulations.
Calcium induced regulation of skeletal troponin--computational insights from molecular dynamics simulations.
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DOI：
10.1371/journal.pone.0058313
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lu H
中科院分区：
文献类型：
--
作者：
Genchev GZ;Kobayashi T;Lu H
钙与横纹肌调节蛋白肌钙蛋白的调节位点之间的相互作用开启和关闭肌肉收缩。在骨骼肌钙蛋白中，钙与TnC亚基的位点I和II结合导致肌钙蛋白复合物中的一系列结构变化，沿沿着肌动蛋白丝置换原肌球蛋白，并允许肌球蛋白-肌动蛋白相互作用产生机械力。在这项研究中，我们使用分子动力学模拟的钙依赖性动力学的快速骨骼肌钙蛋白分子和它的肌钙蛋白C亚基在钙饱和和耗尽状态。我们专注于N叶和描述原子水平的事件发生后，从监管网站I和II的钙离子的去除。主要结构事件-A/B螺旋疏水口袋的闭合由以下构象变化的综合效应引起：位置2、9处残基的主链氮原子与位置12处残基的侧链氧原子之间的H-键相互作用的断裂在位点I和II中的N2- 0 E12/N9- 0 E12）;位点I和II的扩增和位点II N-末端末端区段柔性的增加; β-折叠支架的强化;以及N-半段疏水残基的后续重新包装。此外，钙释放允许N叶相对于Tn分子的其余部分旋转。基于本文提出的研究结果，我们提出了一种新的模型骨骼细丝的调节。
The interaction between calcium and the regulatory site(s) of striated muscle regulatory protein troponin switches on and off muscle contraction. In skeletal troponin binding of calcium to sites I and II of the TnC subunit results in a set of structural changes in the troponin complex, displaces tropomyosin along the actin filament and allows myosin-actin interaction to produce mechanical force. In this study, we used molecular dynamics simulations to characterize the calcium dependent dynamics of the fast skeletal troponin molecule and its TnC subunit in the calcium saturated and depleted states. We focused on the N-lobe and on describing the atomic level events that take place subsequent to removal of the calcium ion from the regulatory sites I and II. A main structural event - a closure of the A/B helix hydrophobic pocket results from the integrated effect of the following conformational changes: the breakage of H-bond interactions between the backbone nitrogen atoms of the residues at positions 2, 9 and sidechain oxygen atoms of the residue at position 12 (N2-OE12/N9-OE12) in sites I and II; expansion of sites I and II and increased site II N-terminal end-segment flexibility; strengthening of the β-sheet scaffold; and the subsequent re-packing of the N-lobe hydrophobic residues. Additionally, the calcium release allows the N-lobe to rotate relative to the rest of the Tn molecule. Based on the findings presented herein we propose a novel model of skeletal thin filament regulation.