Entropy Driving the Mg2+-Induced Folding of TPP Riboswitch RNA
Entropy Driving the Mg2+-Induced Folding of TPP Riboswitch RNA
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熵驱动 Mg2 诱导的 TPP 核糖开关 RNA 折叠
DOI：
10.1021/acs.jpcb.2c03688
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yu Liu
中科院分区：
文献类型：
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作者：
Jun Li;Xiaoyu Zhang;Liang Hong;Yu Liu
众所周知，Mg2+ 可促进 RNA 的结构折叠。然而，Mg2+ 在 RNA 折叠中的热力学和动力学作用仍然难以捉摸。在这里，我们利用单分子荧光共振能量转移（smFRET）和等温滴定量热法（ITC）来研究Mg2+促进焦磷酸硫胺素（TPP）核糖开关RNA折叠的机制。 smFRET 的结果表明，Mg2+ 的存在使 RNA 变得紧密，并扩大了各个 RNA 分子之间的构象分散性，从而导致大量的熵增益。 Mg2+触发的紧凑而灵活的构象可能有助于核糖开关识别其特定配体并进一步折叠。 ITC 实验支持了这一点，其中 Mg2+ 诱导的 RNA 折叠是由熵 (ΔS) 而不是熵 (ΔH) 驱动的。我们的结果补充了对 Mg2+ 诱导的 RNA 折叠的理解。这项工作中开发的策略可用于模拟其他 RNA 在不同条件下的折叠。
Mg2+is well known to facilitate the structural folding of RNA. However, the thermodynamic and dynamic roles of Mg2+in RNA folding remain elusive. Here, we exploit single-molecule fluorescence resonance energy transfer (smFRET) and isothermal titration calorimetry (ITC) to study the mechanism of Mg2+in facilitating the folding of thiamine pyrophosphate (TPP) riboswitch RNA. The results of smFRET identify that the presence of Mg2+compacts the RNA and enlarges the conformational dispersity among individual RNA molecules, resulting in a large gain of entropy. The compact yet flexible conformations triggered by Mg2+may help the riboswitch recognize its specific ligand and further fold. This is supported by the ITC experiments, in which the Mg2+-induced RNA folding is driven by entropy (ΔS) instead of enthalpy (ΔH). Our results complement the understanding of the Mg2+-induced RNA folding. The strategy developed in this work can be used to model other RNAs’ folding under different conditions.