Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan, Hubei, China.
PLoS One. 2012;7(9):e45239. doi: 10.1371/journal.pone.0045239. Epub 2012 Sep 17.
Riboswitches are novel RNA regulatory elements. Each riboswitch molecule consists of two domains: aptamer and express platform. The three-dimensional (3D) structure of the aptamer domain, depending on ligand binding or not, controls that of the express platform, which then switches on or off transcriptional or translational process. Here we study the two types of preQ(1) riboswitch aptamers from T. Tengcongensis (denoted as Tte preQ(1) riboswitch for short below) and Bacillus subtilis (denoted as Bsu preQ(1) riboswitch for short below), respectively. The free-state 3D structure of the Tte preQ(1) riboswitch is the same as its bound state but the Bsu preQ(1) riboswitch is not. Therefore, it is very interesting to investigate how these riboswitches realize their different regulation functions. We simulated the unfolding of these two aptamers through all-atom molecular dynamic simulation and found that they have similar unfolding or folding pathways and ligand-binding processes. The main difference between them is the folding intermediate states. The similarity and difference of their unfolding or folding dynamics may suggest their similar regulation mechanisms and account for their different functions, respectively. These results are also useful to understand the regulation mechanism of other riboswitches with free-state 3D structures similar to their bound states.
Riboswitches 是新型的 RNA 调控元件。每个核糖开关分子由两个结构域组成：适体和表达平台。适体结构域的三维（3D）结构，取决于配体的结合与否，控制着表达平台的结构，从而开启或关闭转录或翻译过程。在这里，我们研究了来自 T. Tengcongensis（简称 Tte preQ(1) 核糖开关）和枯草芽孢杆菌（简称 Bsu preQ(1) 核糖开关）的两种类型的 preQ(1) 核糖开关适体。Tte preQ(1) 核糖开关的自由态 3D 结构与其结合态相同，但 Bsu preQ(1) 核糖开关则不同。因此，研究这些核糖开关如何实现其不同的调节功能非常有趣。我们通过全原子分子动力学模拟模拟了这两个适体的展开过程，发现它们具有相似的展开或折叠途径和配体结合过程。它们之间的主要区别在于折叠中间态。它们展开或折叠动力学的相似性和差异性可能暗示着它们具有相似的调节机制，并分别解释了它们的不同功能。这些结果对于理解具有类似结合态自由态 3D 结构的其他核糖开关的调节机制也很有用。
