Cooperation between Magnesium and Metabolite Controls Collapse of the SAM-I Riboswitch.
Cooperation between Magnesium and Metabolite Controls Collapse of the SAM-I Riboswitch.
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镁和代谢物之间的合作控制 SAM-I 核糖开关的崩溃。
DOI：
10.1016/j.bpj.2017.06.044
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发表时间：
2017
影响因子：
3.4
通讯作者：
Sanbonmatsu,KarissaY
中科院分区：
文献类型：
--
作者：
Roy,Susmita;Onuchic,JoséN;Sanbonmatsu,KarissaY
s -腺苷蛋氨酸(SAM)- 1核糖开关是一种非编码RNA，在代谢产物（SAM）结合的反应中调节转录终止过程。核开关的适体部分可根据代谢物的存在而采取开放或关闭状态。虽然开闭态之间的跃迁对开关过程至关重要，但其原子性细节尚未得到很好的理解。通过原子模拟，我们计算了SAM和镁离子对SAM- 1核开关折叠自由能的影响。这些分子模拟结果与我们之前的湿实验室实验一致，有助于解释SHAPE探测测量结果。在这里，分子动力学模拟明确识别靶RNA基序对镁离子和SAM敏感。在模拟中，我们观察到，尽管代谢物主要稳定P1和P3螺旋，但镁在稳定P2和P4螺旋之间的赝结相互作用中起重要作用，即使在高代谢物浓度下也是如此。镁稳定假结，结合SAM稳定P1，解释了SAM和镁都需要形成SAM- 1核开关的完全折叠代谢物结合的关闭状态。在没有SAM的情况下，假结经常发生从开到闭的构象转变，类似于呼吸。这些假结波动通过促进螺旋P1的5 '端波动来破坏结合位点。镁通过协调假结和5 ' -P1波动，使景观倾向于坍缩状态（预组织）。SAM和镁在稳定重要的三级相互作用方面的合作阐明了它们在转录调控中的功能意义。
The S-adenosylmethionine (SAM)-I riboswitch is a noncoding RNA that regulates the transcription termination process in response to metabolite (SAM) binding. The aptamer portion of the riboswitch may adopt an open or closed state depending on the presence of metabolite. Although the transition between the open and closed states is critical for the switching process, its atomistic details are not well understood. Using atomistic simulations, we calculate the effect of SAM and magnesium ions on the folding free energy landscape of the SAM-I riboswitch. These molecular simulation results are consistent with our previous wetlab experiments and aid in interpreting the SHAPE probing measurements. Here, molecular dynamics simulations explicitly identify target RNA motifs sensitive to magnesium ions and SAM. In the simulations, we observe that, whereas the metabolite mostly stabilizes the P1 and P3 helices, magnesium serves an important role in stabilizing a pseudoknot interaction between the P2 and P4 helices, even at high metabolite concentrations. The pseudoknot stabilization by magnesium, in combination with P1 stabilization by SAM, explains the requirement of both SAM and magnesium to form the fully collapsed metabolite-bound closed state of the SAM-I riboswitch. In the absence of SAM, frequent open-to-closed conformational transitions of the pseudoknot occur, akin to breathing. These pseudoknot fluctuations disrupt the binding site by facilitating fluctuations in the 5′-end of helix P1. Magnesium biases the landscape toward a collapsed state (preorganization) by coordinating pseudoknot and 5′-P1 fluctuations. The cooperation between SAM and magnesium in stabilizing important tertiary interactions elucidates their functional significance in transcription regulation.
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影响因子：
15
作者：
Suddala KC;Wang J;Hou Q;Walter NG
通讯作者：
Walter NG
影响因子：
3.4
作者：
Whitford, Paul C.;Schug, Alexander;Sanbonmatsu, Kevin Y.
通讯作者：
Sanbonmatsu, Kevin Y.
非编码 RNA：细胞中的多任务分子。
影响因子：
5.6
作者：
Gomes AQ;Nolasco S;Soares H
通讯作者：
Soares H
影响因子：
5.6
作者：
Lu C;Ding F;Chowdhury A;Pradhan V;Tomsic J;Holmes WM;Henkin TM;Ke A
通讯作者：
Ke A
影响因子：
14.9
作者：
Huang W;Kim J;Jha S;Aboul-ela F
通讯作者：
Aboul-ela F