中国组织工程研究

中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (16): 2549-2557.doi: 10.3969/j.issn.2095-4344.0237

• 组织构建细胞学实验 cytology experiments in tissue construction • 上一篇    下一篇

NaCl浓度改变对人类神经元钙传感蛋白结构的影响：来自分子动力学模拟证据

朱玉珍1，李云翔1，蔡  皓1，张庆文2   

  1. 1上海师范大学体育学院，上海市  200234；2上海体育学院，上海市  200438
  • 收稿日期:2018-03-12 出版日期:2018-06-08 发布日期:2018-06-08
  • 通讯作者: 蔡皓，教授，上海师范大学体育学院，上海市 200234
  • 作者简介:朱玉珍，女，1978年生，山东省平度市人，汉族，2016年上海体育学院毕业，博士，主要从事运动相关蛋白结构与功能研究。
  • 基金资助:

    上海高校青年教师培养资助项目(A-9103-17-041331)；上海体育学院研究生教育创新科研项目(yjscx2015003)

Variations of sodium chloride concentration affect conformational dynamics of human neuronal calcium sensor-1 protein: a molecular dynamics simulation study

Zhu Yu-zhen1, Li Yun-xiang1, Cai Hao1, Zhang Qing-wen2   

  1. 1Physical Education College, Shanghai Normal University, Shanghai 200234, China; 2Shanghai University of Sport, Shanghai 200438, China
  • Received:2018-03-12 Online:2018-06-08 Published:2018-06-08
  • Contact: Cai Hao, Professor, Physical Education College, Shanghai Normal University, Shanghai 200234, China
  • About author:Zhu Yu-zhen, Ph.D., Physical Education College, Shanghai Normal University, Shanghai 200234, China
  • Supported by:

    the Young Teacher Training Project of Shanghai Universities, No. A-9103-17-041331; the Postgraduate Education Innovative Research Project of Shanghai University of Sport, No. yjscx2015003

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摘要：

文章快速阅读：

文题释义：
神经元钙传感蛋白：是一种能够触发信号转导的蛋白，在学习、记忆、行为探索和物体识别中起到重要的作用，而且在不同的大脑区域、不同环境中表现出不同的生理功能，还能够通过运动训练调节特定的认知过程。
神经元钙传感蛋白分子结构：神经元钙传感蛋白分子结构中包含190个氨基酸，主要由9个α-螺旋(H1-H9)、3个环形结构(L1-L3)和4个EF-hand(EF1-EF4)组成，是一个含有高电荷的蛋白，其中正电荷氨基酸有24个，负电荷氨基酸有33个。
摘要
背景：人类神经元钙传感蛋白是一个含有高电荷的蛋白，对溶液温度极其敏感，但溶液中离子浓度的变化是否能够改变蛋白结构，进而影响其正常功能的发挥，尚未发现相关研究。
目的：探讨溶液中NaCl浓度的微小改变对人类神经元钙传感蛋白结构动力学影响的分子机制。
方法：采用全原子计算机动力学模拟的方法，将蛋白质数据库中ID为2LCP的人类神经元钙传感蛋白前两个能量最低的结构作为初始结构，能量最小化后，将蛋白置于NaCl浓度分别为0.1，0.3和1 mol/L的水溶液中，以高速摄像速度(ps，10-12 s)记录蛋白在模拟体系中的运行和变化情况。
结果与结论：溶液中NaCl浓度升高，①人类神经元钙传感蛋白柔性增加，整体结构和局部的疏水口袋体积增大；②蛋白C端尾部L3蜷缩，首尾氨基酸D176和V190之间的次联系路径数量明显减少，导致两者之间的联系减弱；③蛋白N段和C段氨基酸之间的联系削弱，但两段段内氨基酸联系明显增强；④蛋白正负电荷间形成的盐桥数量和百分比均降低，尤其在0.3 mol/L NaCl水溶液中的减少更为明显。⑤结果说明，人类神经元钙传感蛋白对溶液NaCl浓度的改变非常敏感，NaCl浓度的微小变化能够引起蛋白关键结构的改变，从原子-分子的视角，为人类神经元钙传感蛋白在不同溶液环境中的结构变化提供理论参考。

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程
ORCID: 0000-0002-3327-7976(朱玉珍)

关键词: 人类神经元钙传感蛋白, NaCl浓度, 结构特性, 动态网络分析, 盐桥, 计算机分子动力学模拟

Abstract:

BACKGROUND: Human neuronal calcium sensor-1 (NCS-1) protein with a high charge is extremely sensitive to solution temperature, but whether the change of ion concentration in the solution can change the protein structure and affect the physiological function has not been reported.
OBJECTIVE: To investigate the molecular mechanism of variations of sodium chloride concentration altering conformational dynamics of human NCS-1.
METHODS: Through molecular dynamics simulation, the first two minimum energy models (PDB id: 2LCP) were utilized as the starting states of each independent molecular dynamics simulation of the human NCS-1 protein. After energy minimization, two different initial structures were used to conduct three independent 500 ns molecular dynamics simulations with explicit solvent for human NCS-1 protein at 0.1, 0.3 and 1 mol/L sodium chloride concentration.
RESULTS AND CONCLUSION: The slightly high concentration of sodium chloride increased the flexibility of loop L2, simultaneously expanded the global and local structure of NCS-1 protein. Increase in sodium chloride concentration induced loop L3 to adopt a collapsed state and reduced the connectivity between the starting and ending residues of loop L3. N-domain and C-domain interdomain correlation was weakened and the intradomain coupling strengthened. Formation number and the probability of the salt bridges were reduced dramatically, especially at 0.3 mol/L sodium chloride. These findings manifest that human NCS-1 protein is sensitive to the small variation of sodium chloride concentration, which may alter the key factors on protein conformation. Our study may provide the theoretical reference at the atomic structural insights for probing the conformational variations of human NCS-1 protein at the different aqueous solutions.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Neuronal Calcium-Sensor Proteins, Sodium Chloride, Protein Structure, Quaternary, Kinetics, Computer Simulation, Tissue Engineering

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