College of Chemistry, Chemical Engineering and Materials, Handan University, No. 530 North Xueyuan Road, Hanshan District, Han Dan 056005, Hebei, China.
College of Chemistry, Beijing Normal University, 19# Xinjiekouwai Street, Beijing 100875, China.
Int J Mol Sci. 2018 Nov 9;19(11):3527. doi: 10.3390/ijms19113527.
Riboswtich RNAs can control gene expression through the structural change induced by the corresponding small-molecule ligands. Molecular dynamics simulations and free energy calculations on the aptamer domain of the 3',3'-cGAMP riboswitch in the ligand-free, cognate-bound and noncognate-bound states were performed to investigate the structural features of the 3',3'-cGAMP riboswitch induced by the 3',3'-cGAMP ligand and the specificity of ligand recognition. The results revealed that the aptamer of the 3',3'-cGAMP riboswitch in the ligand-free state has a smaller binding pocket and a relatively compact structure versus that in the 3',3'-cGAMP-bound state. The binding of the 3',3'-cGAMP molecule to the 3',3'-cGAMP riboswitch induces the rotation of P1 helix through the allosteric communication from the binding sites pocket containing the J1/2, J1/3 and J2/3 junction to the P1 helix. Simultaneously, these simulations also revealed that the preferential binding of the 3',3'-cGAMP riboswitch to its cognate ligand, 3',3'-cGAMP, over its noncognate ligand, c-di-GMP and c-di-AMP. The J1/2 junction in the 3',3'-cGAMP riboswitch contributing to the specificity of ligand recognition have also been found.
核糖开关 RNA 可以通过相应小分子配体诱导的结构变化来控制基因表达。对 3'，3'-cGAMP 核糖开关的无配体、同源结合和非同源结合状态的适体结构域进行了分子动力学模拟和自由能计算，以研究 3'，3'-cGAMP 配体诱导的 3'，3'-cGAMP 核糖开关的结构特征和配体识别的特异性。结果表明，无配体状态下的 3'，3'-cGAMP 核糖开关适体的结合口袋较小，结构相对紧凑，而在 3'，3'-cGAMP 结合状态下则较大。3'，3'-cGAMP 分子与 3'，3'-cGAMP 核糖开关的结合通过从包含 J1/2、J1/3 和 J2/3 连接的结合位点口袋到 P1 螺旋的变构通讯诱导 P1 螺旋的旋转。同时，这些模拟还表明，3'，3'-cGAMP 核糖开关优先与其同源配体 3'，3'-cGAMP 结合，而不是与其非同源配体 c-di-GMP 和 c-di-AMP 结合。还发现 3'，3'-cGAMP 核糖开关的 J1/2 连接有助于配体识别的特异性。
