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两种共享一个共同的联结折的核糖突变类在适应突变的能力上表现出很大的差异
Yoshita Srivastava1,2, Olayinka Akinyemi2,3, Tiana C Rohe1,2
1Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave MC 712, Rochester, NY 14642, USA.
Nucleic acids research
|October 16, 2024
概括
与II类不同的是,III类 рибо开关尽管发生了突变,但仍然保持了preQ1结合. 补偿相互作用保留RNA结构,但功能上有害的突变改变了相关的运动.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 结构生物学 结构生物学
背景情况:
- рибо开关是调节基因表达的RNA分子,以应对小分子结合.
- 感知prequeuosine1 (preQ1) 的 рибо开关存在三种不同的类别 (I,II,III),具有不同的结构.
- 第二类和第三类的核糖开关利用保存的核酸进行前Q1代谢物结合,但第二类对结合口袋突变敏感.
研究的目的:
- 为了研究突变对III类 рибо交换机的结构,功能和preQ1结合亲和力的影响.
- 为了比较III类riboswitch与以前研究的II类变体的突变耐受性.
- 阐明弥补相互作用的基础分子机制及其在维护 рибо开关功能中的作用.
主要方法:
- 引入四个等效突变到一个III类核糖突变器中.
- 突变的III类 рибо交换机的共同晶体结构的确定.
- 化学修饰分析和分子动力学 (MD) 模拟.
- 评估细菌中的基因调节活性.
- 主要组件分析 (PCA) 的MD轨迹.
主要成果:
- 在III类 рибо开关中的突变保持了紧密的preQ1结合,与II类相反.
- 共同晶体结构揭示了补偿相互作用,保留了 рибо开关折叠.
- 尽管局部灵活性变化,MD模拟表明突变并没有明显破坏稳定.
- 第三类突变者保留了基因调节活性,而口袋地板突变比墙壁突变更能耐受.
- 有害突变改变了绑定口袋和调节区域之间的长距离相关运动.
结论:
- 补偿相互作用的形成是依赖于Riboswitch折叠中的上下文.
- 三等级的核突变器对结合口袋突变的耐受性比二等级更高.
- 功能上有害的突变可以破坏对基因调节至关重要的远程RNA动态.
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