A mechanism for S-adenosyl methionine assisted formation of a riboswitch conformation: a small molecule with a strong arm.
A mechanism for S-adenosyl methionine assisted formation of a riboswitch conformation: a small molecule with a strong arm.
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DOI：
10.1093/nar/gkp664
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发表时间：
2009-10
影响因子：
14.9
通讯作者：
Aboul-ela F
中科院分区：
文献类型：
--
作者：
Huang W;Kim J;Jha S;Aboul-ela F
s -腺苷甲硫氨酸-1 （SAM- 1）核开关在SAM结合时通过形成替代构象介导参与硫代谢的蛋白质表达。在结合构象中的RNA的动力学捕获模型需要在转录暂停期间退火非相邻的mRNA片段。将不相邻的片段聚集在一起所需的熵成本应该会减缓折叠过程。为了解决这一矛盾，我们从SAM结合RNA的x射线坐标开始，对SAM- 1核开关适体域进行了分子动力学模拟。单个轨迹为200纳秒，是这种大小的RNA所报道的最长轨迹之一。我们应用主成分分析（PCA）来探讨这两种轨迹之间的全球动力学差异。我们观察到在SAM存在下非相邻二核苷酸的堆叠和非堆叠状态之间的构象转换。在没有SAM的情况下，结合的镁离子与二核苷酸堆栈中涉及的核苷酸之一A9的磷酸盐之间的配位不稳定。静电电位图揭示了在SAM存在时Mg结合位点的“热点”。这些结果表明，SAM结合有助于以有利于P1螺旋形成的方式定位J1/2。
The S-adenosylmethionine-1 (SAM-I) riboswitch mediates expression of proteins involved in sulfur metabolism via formation of alternative conformations in response to binding by SAM. Models for kinetic trapping of the RNA in the bound conformation require annealing of nonadjacent mRNA segments during a transcriptional pause. The entropic cost required to bring nonadjacent segments together should slow the folding process. To address this paradox, we performed molecular dynamics simulations on the SAM-I riboswitch aptamer domain with and without SAM, starting with the X-ray coordinates of the SAM-bound RNA. Individual trajectories are 200 ns, among the longest reported for an RNA of this size. We applied principle component analysis (PCA) to explore the global dynamics differences between these two trajectories. We observed a conformational switch between a stacked and nonstacked state of a nonadjacent dinucleotide in the presence of SAM. In the absence of SAM the coordination between a bound magnesium ion and the phosphate of A9, one of the nucleotides involved in the dinucleotide stack, is destabilized. An electrostatic potential map reveals a ‘hot spot’ at the Mg binding site in the presence of SAM. These results suggest that SAM binding helps to position J1/2 in a manner that is favorable for P1 helix formation.
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