G-Quadruplex conformational change driven by pH variation with potential application as a nanoswitch.
G-Quadruplex conformational change driven by pH variation with potential application as a nanoswitch.
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DOI：
10.1016/j.bbagen.2013.06.019
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发表时间：
2013-10
期刊：
影响因子：
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通讯作者：
Yi-yong Yan;Jia-Heng Tan;Yu-jing Lu;Siu-cheong Yan;Kwok‐yin Wong;Ding Li;L. Gu;Zhishu Huang
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文献类型：
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作者：
Yi-yong Yan;Jia-Heng Tan;Yu-jing Lu;Siu-cheong Yan;Kwok‐yin Wong;Ding Li;L. Gu;Zhishu Huang
研究背景G-四链体是一种高度多态性的结构，其在酸性条件下的行为尚未得到很好的研究。用CD熔融法测定了G-四链体的热稳定性。利用CD动力学研究了互变动力学曲线。在pH变化和丙烯酰胺淬灭期间监测插入的2-氨基嘌呤（Ap）的荧光，指示环的状态。结果G-四链体的特异性环能随pH值的变化而发生构象变化。这种转化是由环重排引起的。通过对不同G-四链体的文库筛选，发现了一个具有最佳转化特性的序列，并基于该序列构建了一个pH驱动的三档纳米开关.ConclusionsCertain G-四链体在低pH下发生构象变化，Loop是控制pH变化时相互转化的决定性因素.具有TT中心环的G-Quadruplex可以在比具有TTA环的G-Quadruplex更温和的条件下转化。这些结果为研究G-四链体的多态性提供了更多的信息，也为基于DNA的纳米机器和逻辑门的设计提供了参考。
BackgroundG-Quadruplex is a highly polymorphic structure, and its behavior in acidic condition has not been well studied.MethodsCircular dichroism (CD) spectra were used to study the conformational change of G-quadruplex. The thermal stabilities of the G-quadruplex were measured with CD melting. Interconversion kinetics profiles were investigated by using CD kinetics. The fluorescence of the inserted 2-Aminopurine (Ap) was monitored during pH change and acrylamide quenching, indicating the status of the loop. Proton NMR was adopted to help illustrate the change of the conformation.ResultsG-Quadruplex of specific loop was found to be able to transform upon pH variation. The transformation was resulted from the loop rearrangement. After screening of a library of diverse G-quadruplex, a sequence exhibiting the best transformation property was found. A pH-driven nanoswitch with three gears was obtained based on this transition cycle.ConclusionsCertain G-quadruplex was found to go through conformational change at low pH. Loop was the decisive factor controlling the interconversion upon pH variation. G-Quadruplex with TT central loop could be converted in a much milder condition than the one with TTA loop. It can be used to design pH-driven nanodevices such as a nanoswitch.General significanceThese results provide more insights into G-quadruplex polymorphism, and also contribute to the design of DNA-based nanomachines and logic gates.