调节RNA环动力学和亚基因组 Flaviviral RNA中的折叠
Avijit Mainan1, Rimi Kundu1, Rishabh K Singh1
1Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal 741246, India.
The journal of physical chemistry. B
|September 30, 2024
概括
这项研究揭示了离子 (Mg2+) 如何对蚊子传播的黄病毒RNA结构 (xrRNA1) 的折叠至关重要. Mg2+稳定关键相互作用,使RNA能够抵抗宿主酶的降解,这对病毒复制至关重要.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 生物物理学的生物物理.
背景情况:
- 蚊子传播的黄病毒产生亚基因组RNA,包括xrRNA1,它具有伪结 (PK) 结构,对宿主外核酶XRN1.1产生抗性.
- 了解xrRNA1折叠及其与离子的相互作用对于理解病毒RNA稳定性和宿主-病原体相互作用至关重要.
研究的目的:
- 为了研究 counterions,特别是 K+ 和 Mg2+ 在 xrRNA1 结构折叠中的作用.
- 使用先进的计算方法阐明xrRNA1的折叠机制和形状动态.
主要方法:
- 广泛的明确溶剂分子动力学 (MD) 模拟来描述RNA离子环境.
- 基于全原子结构的RNA模型与混合隐式-显式离子处理和动态对子离子凝结模型来探索折叠路径.
- 自由能量模拟和光学笔实验,以验证折叠路径和形状平衡.
主要成果:
- 确定了特定的RNA-Mg2+相互作用,包括内球/化和外球协调.
- 揭示了xrRNA1的潜在折叠路径,与实验数据一致.
- 证明Mg2+离子将平衡转向近环状态,通过桥接G50和A33.3稳定远程PK相互作用.
结论:
- 2+在稳定xrRNA1的远程PK结构方面发挥着关键作用,这对于其抵抗XRN1降解至关重要.
- 通过Mg2+介导的G50-A33相互作用是控制RNA的环开和环闭形态转换的关键.
- 这种对Mg2+依赖RNA折叠的理解可以为提高flaviviral xrRNAs中Xrn1抗性的强度的策略提供信息.
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