用于外链结合进行重塑的结合体结构
Sebastian M Fica1, Chris Oubridge1, Wojciech P Galej1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Nature
|January 12, 2017
概括
在分支和外链结合阶段之间,结合体会发生重大结构变化. 一个新的冷电子显微镜结构揭示了分支螺旋是如何旋转的,使得3'外核对接并为mRNA拼接做准备.
科学领域:
- 分子生物学
- 结构生物学
- 进行RNA处理
背景情况:
- 结合体是一个大型分子机器,负责从前传递 RNA (前mRNA) 中去除内子.
- 拼接是通过两个连续的转化反应发生的,由拼接体内的U6小核RNA (snRNA) 催化.
- 之前的结构捕获了C复合体中的结合体,显示了分支因子如何将前mRNA定位为第一个催化步骤.
研究的目的:
- 在第一个催化步骤 (分支) 和第二个催化步骤 (外接) 之前阐明结合体的结构重组.
- 了解特定蛋白质和RNA元素在促进这两个关键拼接阶段之间的转换中的作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了Saccharomyces cerevisiae结合体的结构.
- 该结构在3.8 Å分辨率下得到解析,捕获了由Prp16依赖ATP重塑后停滞不前的C*复合体状态.
- 对现有的C复合结构进行了比较分析,以确定形状变化.
主要成果:
- 与Prp8相关的U6 snRNA催化核仍然存在,但与C复合体相比,分支螺旋经历了显著的75°旋转.
- 这种旋转由Prp17,Cef1和重定向的Prp8 RNase H-like域稳定,将分支腺素从催化核心重新定位.
- 重定位的分支螺旋为3'外因子创造了空间,并与U6 snRNA重组了5'拼接位的相互作用,而Slu7和Prp18则与Prp8结合以进行外因子结合.
结论:
- C* 综合体的冷-EM 结构揭示了从mRNA前分支到外链结合的转变至关重要的一种独特的结合体构造.
- 蛋白质介导的重塑,特别是分支螺旋的旋转,对于为第二个催化步骤准备spliceosome至关重要.
- 这些发现与C复合结构一起,说明了spliceosome在其催化周期中的动态构造变化.
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