高通量模拟揭示了酒精对MSCL膜的介导作用
Manuel N Melo1,2, Clément Arnarez1,2, Hendrik Sikkema1,2
1Groningen Biomolecular Science and Biotechnology Institute, University of Groningen , Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
Journal of the American Chemical Society
|January 27, 2017
概括
大导电性的机械敏感通道 (MscL) 作为细胞应急. 酒精通过改变膜环境而改变MscL结合,而不是通过特定的结合部位,这是模拟和实验证实的.
科学领域:
- 生物物理
- 计算生物学
- 膜蛋白研究
背景情况:
- 大导电性的机械敏感通道 (MscL) 是重要的细菌膜蛋白.
- 在透应激过程中, MscL 作为紧张门离子通道, 作为细胞"应急释放".
- MscL对其膜环境的敏感性使其成为研究膜蛋白与细胞间相互作用的优秀模型.
研究的目的:
- 研究不同双层环境,特别是酒精暴露对MscL门动力学的影响.
- 通过计算模拟阐明酒精如何影响 MscL 通道功能.
- 用实验数据验证在的预测.
主要方法:
- 在各种脂质双层组合中模拟MscL的高通量粗粒分子动力学.
- 酒精度的系统变化 (乙醇,八醇,十二醇,六醇).
- 实验验证使用复制的MscL脂质体光流量测定.
主要成果:
- 乙醇,八醇和十二醇的开放时间增加,但六醇的开放时间没有增加.
- 八醇对 MscL 的抑制作用在高达 10 - 20 摩尔 % 的度下加剧.
- 模拟显示酒精效应源于改变的双层特性和 MscL-双层接口,而不是特定的结合点.
结论:
- 两层性质的酒精诱导的修改显著影响了 MscL 门的动力学.
- 这项研究证明了广泛的分子模拟在预测由于环境变化的膜蛋白的功能变化方面的力量.
- 这些发现提供了对膜组成如何影响机械敏感通道功能的机制学理解.
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