聚皮里米丁通道结合蛋白的N终端域是适应性RNA识别的动态折叠平台
Fred F Damberger1,2, Miroslav Krepl3, Rajika Arora1
1Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland.
Nucleic acids research
|August 24, 2024
概括
聚皮里米丁管结合蛋白 (PTB) 使用其RRM1域结合结构RNA. 这种结合会诱导PTB的动态变化.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- 聚胺系结合蛋白 (PTB) 通过RNA结合来调节基因表达.
- PTB的N端RNA识别动机域 (RRM1) 具有C端螺旋 (α3),这对其功能至关重要.
- 螺旋α3与RNA的相互作用是间接的,这表明有一个全性调节机制.
研究的目的:
- 为了研究干环RNA和PTB的RRM1域之间的动态适应过程.
- 阐明由螺旋体α3.3.介导的全调节的机械基础.
- 了解RNA结合如何影响PTB的RRM1域的结构动态.
主要方法:
- 核磁共振 (NMR) 光谱法用于确定蛋白质结构和动态.
- 分子动力学 (MD) 模拟以建模蛋白质-RNA相互作用.
- 实验室内核糖体进入部位 (IRES) 测试以评估PTB功能.
主要成果:
- 自由RRM1表现出螺旋α3.3的部分排序和短暂相互作用.
- RNA结合导致螺旋体α3的排序,并灭快速动态,在接口上有微秒的残余动态.
- MD模拟显示了RRM1-RNA结合,状α3稳定和RNA序列信息转导成α3形状变化之间的合.
- 功能性测试表明,改变的α3动态影响了PTB在IRES介导的翻译中的作用.
结论:
- 在结合结构RNA时,PTB的RRM1域经历了显著的动态重组.
- 螺旋α3作为一个关键的全调节剂,将RNA结合事件转化为形状变化.
- 涉及状体α3的动态性对PTB在基因表达中的调节功能至关重要.
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