Shandong Key Laboratory of Biophysics, Dezhou University, Dezhou 253023, China.
College of Computer and Information Engineering, Dezhou University, Dezhou 253023, China.
J Chem Inf Model. 2024 Oct 14;64(19):7555-7564. doi: 10.1021/acs.jcim.4c00852. Epub 2024 Sep 29.
Riboswitches regulate downstream gene expression by binding to specific small molecules or ions with multiple mechanisms to transfer the binding information. In the case of the fluoride riboswitch, the transcription termination signal is conveyed through a transient excited state (ES). In this work, we performed conventional molecular dynamics (MD) simulations, totaling 180 μs, to obtain the ES structure and investigate the mechanism underlying information transmission in Mg/F binding within the fluoride riboswitch aptamer. The Mg/F binding pocket exhibits various conformations in its apo form. A series of ES structures were extracted from the MD trajectories of the apo form. The dynamics of the Mg/F binding pocket influenced key pair A40-U48 in ES structures. The pathway connecting the binding pocket to the pair involves interactions between the phosphate groups of U7 and G8 and the nucleobases of G8-C47-U48. Our work presents a structural ensemble of the ES and elucidates a pathway for transferring Mg/F binding information, thereby facilitating the understanding of how the holo-like apo state achieves transcriptional repression.
核糖开关通过多种机制结合特定的小分子或离子来调节下游基因表达，从而传递结合信息。在氟化物核糖开关的情况下，转录终止信号通过瞬态激发态 (ES) 传递。在这项工作中，我们进行了常规的分子动力学 (MD) 模拟，总计 180 μs，以获得 ES 结构，并研究了 Mg/F 在氟化物核糖开关适体结合过程中信息传递的机制。Mg/F 结合口袋在apo 形式下表现出各种构象。从 apo 形式的 MD 轨迹中提取了一系列 ES 结构。Mg/F 结合口袋的动力学影响 ES 结构中关键对 A40-U48。连接结合口袋和碱基对的途径涉及 U7 和 G8 的磷酸基团与 G8-C47-U48 的碱基之间的相互作用。我们的工作展示了 ES 的结构组合，并阐明了传递 Mg/F 结合信息的途径，从而有助于理解类似全酶的 apo 状态如何实现转录抑制。
