以为媒介控制S100蛋白质:通过激发器/信号阻断机制进行体通信
Yiming Xiao1, Gary S Shaw1, Lars Konermann1
1Department of Chemistry, The University of Western Ontario , London, Ontario N6A 5B7, Canada.
Journal of the American Chemical Society
|August 1, 2017
概括
离子阻止S100A11蛋白结合部位的关闭,揭示了一个新的全性机制. 一个不稳定的盐桥启动信号传播,结合块,挑战传统的全性通路模型.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 蛋白质动力学 蛋白质动力学
背景情况:
- 菌蛋白通过信号传输来调节生物过程.
- 全精子调节的精确机制,特别是信号传播,尚未完全理解.
- S100A11是一种二元EF手蛋白,具有Ca2+调节的标结合.
研究的目的:
- 为了阐明S100A11-annexin (Ax) 相互作用的全性机制.
- 了解Ca2+如何控制S100A11目标结合位点的打开和关闭.
- 为了识别全信号传播途径中的初始事件.
主要方法:
- 在显式水中微秒分子动力学 (MD) 模拟.
- -交换质谱仪 (HDX/MS). 交换质谱仪 (HDX/MS) 是一种用于测量和的方法.
- 蛋白质-Ca2+-复合物的计算建模.
主要成果:
- 对S100A11的Ca2+结合防止了目标结合部位的关闭,保持了开放状态.
- 在没有Ca2+的情况下,S100A11目标结合位点关闭,排除了附录素相互作用.
- 一个不稳定的盐桥,而不是化点,启动了导致结合点关闭的全信号级联.
结论:
- 与S100A11结合的Ca2+起到守门员的作用,通过固关键蛋白质元素来防止全信号传输.
- 性通路起源于一个不稳定的盐桥,破坏邻近残留物的稳定.
- 这种机制挑战了在效应体结合部位启动全性通路的传统观点.
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