优化的外围-核心接口增加了Bacillus subtilis glmS ribozyme的适应性
Li-Eng D Yu1, Elise N White2, Sarah A Woodson3
1Program in Cell, Molecular and Developmental Biology and Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
Nucleic acids research
|September 25, 2024
概括
了解核糖酶进化揭示了RNA结构如何影响功能. 破坏自我组装或创造非本地结构的突变降低了 ribozyme 的活性,限制了 RNA 的进化.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
背景情况:
- рибо酶是功能性RNA,具有保存的催化核心和可变的外围域.
- 了解核心-外围相互作用对于 ribozyme 适应性和进化至关重要.
研究的目的:
- 为了研究核心-外围相互作用如何影响 ribozyme 适应性.
- 为了绘制Bacillus subtilis glmS ribozyme中的每个部位的生物化学重要性.
主要方法:
- 高通量测序 (k-seq) 用于测量所有单基替代的裂变动力学.
- 在体外活动测试和折叠实验.
- 所有原子的分子动力学模拟.
主要成果:
- 在体外活动地图与遗传学序列的保存相关.
- 大多数有害突变通过阻碍核糖酶自我组装而降低活性.
- 模拟显示突变会产生破坏催化中心的非本地接口.
结论:
- 生物适应性准确地反映了 ribozymes 在生物化学上重要的位置.
- 由于需要防止非本地螺旋包装,RNA三级结构进化受到限制.
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