Nucleotides adjacent to the ligand-binding pocket are linked to activity tuning in the purine riboswitch.
Nucleotides adjacent to the ligand-binding pocket are linked to activity tuning in the purine riboswitch.
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DOI：
10.1016/j.jmb.2013.02.023
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发表时间：
2013-05-27
影响因子：
5.6
通讯作者：
Batey, Robert T.
中科院分区：
文献类型：
--
作者：
Stoddard, Colby D.;Widmann, Jeremy;Trausch, Jeremiah J.;Marcano-Velazquez, Joan G.;Knight, Rob;Batey, Robert T.
核糖开关RNA直接检测细胞内代谢物浓度为维持代谢动态平衡提供了一种经济而快速的手段。由于许多生物使用同一类核糖开关来控制不同的基因或转录单位，因此很可能在核糖开关中存在功能变异，从而调节活动以满足细胞需求。利用生物信息学方法，我们已经确定了嘌呤核糖开关适配子区域的一个区域，该区域显示了与核糖开关活性相关的保守模式。该区域内的适配子结构域组成可分为9个类别，显示出一系列活性。该区域的天然组成有利于配基结合的快速缔合速率常数和缓慢的解离速率常数。利用X射线结晶学和化学探测，我们证明了自由态和束缚态都受到这一区域的组成的影响，并且适度的序列改变对活性有很大的影响。非天然成分的引入导致无法调节体内的基因表达，这表明适配子结构域的活性是高度可塑性的，因此很容易调节以满足细胞的需要。
Direct sensing of intracellular metabolite concentrations by riboswitch RNAs provides an economical and rapid means to maintain metabolic homeostasis. Since many organisms employ the same class of riboswitch to control different genes or transcription units, it is likely that functional variation exists in riboswitches such that activity is tuned to meet cellular needs. Using a bioinformatic approach, we have identified a region of the purine riboswitch aptamer domain that displays conservation patterns linked to riboswitch activity. Aptamer domain compositions within this region can be divided into nine classes that display a spectrum of activities. Naturally occurring compositions in this region favor rapid association rate constants and slow dissociation rate constants for ligand binding. Using X-ray crystallography and chemical probing, we demonstrate that both the free and bound states are influenced by the composition of this region and that modest sequence alterations have a dramatic impact on activity. The introduction of non-natural compositions result in the inability to regulate gene expression in vivo, suggesting that aptamer domain activity is highly plastic and thus readily tunable to meet cellular needs.
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影响因子：
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作者：
Gilbert, Sunny D.;Mediatore, Sarah J.;Batey, Robert T.
通讯作者：
Batey, Robert T.
影响因子：
14.9
作者：
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作者：
通讯作者：
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影响因子：
6.1
作者：
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通讯作者：
Batey, Robert T.
影响因子：
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作者：
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