Atomistic basis for the on-off signaling mechanism in SAM-II riboswitch.
Atomistic basis for the on-off signaling mechanism in SAM-II riboswitch.
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DOI：
10.1093/nar/gkp1106
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发表时间：
2010-03
影响因子：
14.9
通讯作者：
Hamelberg D
中科院分区：
文献类型：
--
作者：
Kelley JM;Hamelberg D
许多细菌基因由称为核糖开关的代谢物传感基序控制，通常位于其mRNA的5′非翻译区。小分子代谢物以惊人的特异性结合核糖开关的适体结构域，由于表达平台中诱导的构象变化而在反馈环中调节基因调控。在这里，我们报告的S-腺苷甲硫氨酸（SAM）-II核糖开关，参与调节细菌中的硫代谢途径的翻译的分子动力学模拟研究的结果。我们表明，未结合形式的SAM-II核糖开关的构象的合奏是一个松散的假结结构，定期访问类似的绑定形式的构象，和假结结构只有完全形成后结合的代谢产物，SAM。形成与结合形式中的接触类似的未结合形式中的接触的速率是快的。配体与SAM-II的结合改变了表达平台的曲率和碱基配对，这可能影响后者与核糖体的相互作用。
Many bacterial genes are controlled by metabolite sensing motifs known as riboswitches, normally located in the 5′ un-translated region of their mRNAs. Small molecular metabolites bind to the aptamer domain of riboswitches with amazing specificity, modulating gene regulation in a feedback loop as a result of induced conformational changes in the expression platform. Here, we report the results of molecular dynamics simulation studies of the S-adenosylmethionine (SAM)-II riboswitch that is involved in regulating translation in sulfur metabolic pathways in bacteria. We show that the ensemble of conformations of the unbound form of the SAM-II riboswitch is a loose pseudoknot structure that periodically visits conformations similar to the bound form, and the pseudoknot structure is only fully formed upon binding the metabolite, SAM. The rate of forming contacts in the unbound form that are similar to that in the bound form is fast. Ligand binding to SAM-II alters the curvature and base-pairing of the expression platform that could affect the interaction of the latter with the ribosome.