Hierarchical Conformational Dynamics Confers Thermal Adaptability to preQ(1) RNA Riboswitches
Hierarchical Conformational Dynamics Confers Thermal Adaptability to preQ(1) RNA Riboswitches
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分层构象动力学赋予 preQ(1) RNA 核糖开关热适应性
DOI：
10.1016/j.jmb.2020.06.002
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发表时间：
2020
影响因子：
5.6
通讯作者：
Tang Chun
中科院分区：
文献类型：
--
作者：
Gong Zhou;Yang Shuai;Dong Xu;Yang Qing-Fen;Zhu Yue-Ling;Xiao Yi;Tang Chun
单链非编码调控RNA，如细菌核糖开关，是高度动态的。构象动力学使核糖开关在适当的条件下达到最大的开关效率。在这里，我们表征了不同温度下嗜中性菌和嗜热菌的前Q1核糖开关的构象动力学。综合使用小角X射线散射、核磁共振和分子动力学模拟，我们模拟了没有或有配体结合的前Q1核糖开关适配子的系综结构。我们证明了前Q1核糖开关是足够动态的，并且只有在微生物的生理温度附近才能在多个折叠中间体之间波动。RNA的分级折叠动力学包括3‘-尾的对接形成第二个RNA螺旋和螺旋堆积形成H型假结结构。进一步地，我们证明了RNA的二级和三级动力学可以被温度和内环的长度所调制。RNA折叠中间体之间的耦合平衡是预Q1结合所必需的，四态交换模型可以解释配体触发的开关效率随温度的变化。我们一起建立了层次动力学和核糖开关功能之间的关系，并说明了RNA如何适应高温。
Single-stranded noncoding regulatory RNAs, as exemplified by bacterial riboswitches, are highly dynamic. The conformational dynamics allow the riboswitch to reach maximum switching efficiency under appropriate conditions. Here we characterize the conformational dynamics of preQ1riboswitches from mesophilic and thermophilic bacterial species at various temperatures. With the integrative use of small-angle X-ray scattering, NMR, and molecular dynamics simulations, we model the ensemble-structures of the preQ1riboswitch aptamers without or with a ligand bound. We show that the preQ1riboswitch is sufficiently dynamic and fluctuating among multiple folding intermediates only near the physiological temperature of the microorganism. The hierarchical folding dynamics of the RNA involves the docking of 3′-tail to form a second RNA helix and the helical stacking to form an H-type pseudoknot structure. Further, we show that RNA secondary and tertiary dynamics can be modulated by temperature and by the length of an internal loop. The coupled equilibria between RNA folding intermediates are essential for preQ1binding, and a four-state exchange model can account for the change of ligand-triggered switching efficiency with temperature. Together, we have established a relationship between the hierarchical dynamics and riboswitch function, and illustrated how the RNA adapts to high temperature.