Confined space facilitates G-quadruplex formation
Confined space facilitates G-quadruplex formation
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DOI：
10.1038/nnano.2017.29
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发表时间：
2017-06-01
影响因子：
38.3
通讯作者：
Mao, Hanbin
中科院分区：
文献类型：
--
作者：
Shrestha, Prakash;Jonchhe, Sagun;Mao, Hanbin
分子模拟表明，由于熵效应，折叠大分子在受限空间中的稳定性增加。然而，由于受限的分子结构和容器壁之间的相互作用，这种预测缺乏明确的实验证据。在这里，使用DNA折纸纳米笼，我们展示了有限空间对单个人类端粒DNA G-四链体的性质的纯粹影响。我们诱导有针对性的机械展开的G-四链体，而离开纳米笼不受干扰。我们发现，机械和热力学稳定性的G-四链体内的纳米笼的增加，减少笼的大小。与稀释或分子拥挤的缓冲溶液相比，纳米笼内的G-四链体明显更稳定，显示出快100倍的折叠速率。我们的研究结果表明，在细胞中的聚合酶机制内的G-四链体的共复制或共转录折叠的可能性。
Molecular simulations suggest that the stability of a folded macromolecule increases in a confined space due to entropic effects. However, due to the interactions between the confined molecular structure and the walls of the container, clear-cut experimental evidence for this prediction is lacking. Here, using DNA origami nanocages, we show the pure effect of confined space on the property of individual human telomeric DNA G-quadruplexes. We induce targeted mechanical unfolding of the G-quadruplex while leaving the nanocage unperturbed. We find that the mechanical and thermodynamic stabilities of the G-quadruplex inside the nanocage increase with decreasing cage size. Compared to the case of diluted or molecularly crowded buffer solutions, the G-quadruplex inside the nanocage is significantly more stable, showing a 100 times faster folding rate. Our findings suggest the possibility of co-replicational or co-transcriptional folding of G-quadruplex inside the polymerase machinery in cells.