触发因子通过动力捕捉减缓了同翻译折叠,同时对新生链进行了硬质性保护,防止异常的细胞交互
Edward P O'Brien1, John Christodoulou, Michele Vendruscolo
1Department of Chemistry, University of Cambridge, Cambridge, UK.
Journal of the American Chemical Society
|June 12, 2012
概括
大肠杆菌中的触发因子 (TF) 监护人不会改变小蛋白质的折叠,而是通过动态捕获它们来减缓较大的蛋白质. 这通过减少重新排列率,增加道长度和链条纠而发生.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 计算生物学是一种计算生物学.
背景情况:
- 触发因子 (TF) 是一种大肠杆菌的陪伴者,它结合了从核糖体中出现的新生的多链.
- TF可以促进小蛋白域的共同翻译折叠,但会减缓较大的蛋白质的折叠.
- 由于实验的局限性,TF对蛋白质折叠动力学和热力学的确切机制和影响仍然不清楚.
研究的目的:
- 通过分子模拟,研究TF对小和大蛋白域的共同翻译折叠的影响.
- 确定TF是否通过动力或热力学机制改变折叠特性或影响折叠速率.
- 阐明TF延迟较大的蛋白质折叠的特定机制.
主要方法:
- 使用粗粒度模型利用分子模拟.
- 模拟带有和没有TF的核糖体新生链复合体.
- 分析了小蛋白G域和大β-银酸酶域的共同翻译折叠路径.
主要成果:
- TF并没有显著改变小蛋白G域的共同翻译折叠.
- TF显著延迟了大β-银酸酶域的折叠.
- 由于TF诱导的延迟是由于通过减少重新排列率,增加有效的出口道长度和新生的链纠来捕捉展开的合奏的动态陷.
结论:
- TF与新生链的相互作用可以导致动力捕获,特别是对于较大的蛋白质.
- 这种捕获机制涉及减少内部结构重组,从核糖体出口道的固体障碍,以及与TF的物理纠.
- TF介导的捕获代表了促进协译折叠和通过屏蔽多链来防止聚合或降解之间的平衡.
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