Destabilization of i-Motif by Submolar Concentrations of a Monovalent Cation
Destabilization of i-Motif by Submolar Concentrations of a Monovalent Cation
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DOI：
10.1021/jp500120d
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发表时间：
2014-05-08
影响因子：
3.3
通讯作者：
Hong, Seok-Cheol
中科院分区：
文献类型：
--
作者：
Kim, Sung Eun;Lee, Il-Buem;Hong, Seok-Cheol
反离子对于核酸的自组装至关重要。亚摩尔单价阳离子通常被认为通过静电排斥的屏蔽来稳定核酸中的各种类型的碱基对，例如沃森-克里克和胡格斯汀碱基对。除了单价阳离子，酸性pH是i基序形成所需的，因为质子促进胞嘧啶之间的配对。在这里，我们报告说，Li+离子不稳定的i-基序，而其他一价阳离子，Na+和K+，具有通常的稳定效果。然而，热力学数据本身不能揭示哪种机制，增强的展开或抑制折叠或两者兼而有之，是负责Li+诱导的不稳定。为了获得进一步的了解，我们研究了i-基序的动力学。为了处理i基序的缓慢动力学，我们开发了一种称为HaRP的方法来构建长FRET时间轨迹以观察足够数量的转换。我们的动力学分析清楚地表明，Li+离子促进展开的i-基序，但不妨碍其折叠，贷款强有力的支持，我们的假设，这种不寻常的影响Li+的起源。尽管Li+离子的亚埃尺寸允许它们与质子竞争渗透胞嘧啶之间的空间，但它们不能充分地实现质子在介导胞嘧啶对的氢键中的作用。
Counterions are crucial for self-assembly of nucleic acids. Submolar monovalent cations are generally deemed to stabilize various types of base pairs in nucleic acids such as Watson-Crick and Hoogsteen base pairs via screening of electrostatic repulsion. Besides monovalent cations, acidic pH is required for i-motif formation because protons facilitate pairing between cytosines. Here we report that Li+ ions destabilize i-motif, whereas other monovalent cations, Na+ and K+, have the usual stabilizing effect. The thermodynamics data alone, however, cannot reveal which mechanism, enhanced unfolding or suppressed folding or both, is responsible for the Li+-induced destabilization. To gain further insight, we examined the kinetics of i-motif. To deal with slow kinetics of i-motif, we developed a method dubbed HaRP to construct a long FRET time trace to observe a sufficient number of transitions. Our kinetics analysis shows clearly that Li+ ions promote unfolding of i-motif but do not hinder its folding, lending strong support for our hypothesis on the origin of this unusual effect of Li+. Although the subangstrom size of Li+ ions allows them to infiltrate the space between cytosines in competition with protons, they cannot adequately fulfill the role of protons in mediating the hydrogen bonding of cytosine pairs.