蛋白质折叠的新情景可以发生在核糖体上
Edward P O'Brien1, John Christodoulou, Michele Vendruscolo
1Department of Chemistry, Lensfield Road, University of Cambridge, Cambridge CB2 1EW, United Kingdom.
Journal of the American Chemical Society
|January 6, 2011
概括
与溶液相比,蛋白质折叠在核糖体上显著不同. 核糖体破坏原生状态并改变折叠路径,影响合成期间的蛋白质结构和动态.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 蛋白质折叠对于细胞功能至关重要.
- 了解细胞内部的蛋白质折叠,特别是核糖体上的蛋白质折叠,仍然是一个挑战.
- 折叠环境的差异 (散装溶液与细胞) 可以导致不同的蛋白质结构.
研究的目的:
- 研究和阐明在散装溶液中的蛋白质折叠和在核糖体细胞环境中的差异.
- 分析核糖体的表面和出口道如何影响蛋白质折叠动力学和热力学.
- 为了比较不同合成阶段新生链的折叠行为.
主要方法:
- 使用Langevin动力学的模拟.
- 建模完整的核糖体与五个不同的新生链在各种合成阶段被捕.
- 对折叠和展开轨迹,过渡状态组合和折叠路径多样性的分析.
主要成果:
- 核糖体通过增加未折叠状态和减少原始状态来破坏原生蛋白质状态的稳定.
- 新生链表现出改变的折叠合作性,并在核糖体附近采用异构形状.
- 折叠率随着新生的链条长度线性增加,而展开率下降,较大的折叠更容易受到影响.
- 核糖体相互作用驱动过渡状态组合向紧缩和原生类结构.
- 折叠途径变得不那么多样化,有利于在核糖体上启动N端.
结论:
- 核糖体显著扰乱蛋白质折叠,导致与散装溶液相比不同的折叠场景.
- 这些发现适用于停止和连续翻译,只要折叠比单体加法更快.
- 核糖体对蛋白质折叠的诱导影响很大,影响了折叠过程的多个方面.
相关概念视频
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