Structure and Conformational Dynamics of a Stacked Dimeric G-Quadruplex Formed by the Human CEB1 Minisatellite
Structure and Conformational Dynamics of a Stacked Dimeric G-Quadruplex Formed by the Human CEB1 Minisatellite
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DOI：
10.1021/ja4125274
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发表时间：
2014-04-30
影响因子：
15
通讯作者：
Anh Tuan Phan
中科院分区：
文献类型：
--
作者：
Adrian, Michael;Ang, Ding Jie;Anh Tuan Phan
CEB 1是一个高度多态的人类小卫星。在酵母中，CEB 1串联阵列的大小变化与基序形成G.四路在这里，我们报告的NMR溶液结构的G-四链体形成的CEB 1 DNA G-丰富的片段d（AGGGGGGAGGGAGGGTGG），窝藏几个G-tracts，包括一个与六个连续的鸟嘌呤。该序列形成涉及两个亚基堆叠的二聚G-四链体，每个亚基是具有三个G-四分体层、三个双链反转环和一个V形环的独特的快速回复平行链支架。这两个亚基在它们的S '端四联体处堆叠，并且由于堆叠界面处的高度对称性，可能存在多个堆叠旋转异构体。在毫秒时间尺度上存在构象交换，涉及六鸟嘌呤束的两个碱基之间的交换运动。我们的研究结果不仅增加了对人类小卫星中G-四链体形成如何导致遗传不稳定性的理解，而且还解决了关于G-四链体堆叠以及长的连续G-道如何参与G-四链体的结构和构象动力学的基本问题。
CEB1 is a highly polymorphic human minisatellite. In yeast, the size variation of CEB1 tandem arrays has been associated with the capacity of the motif to form G. quadruplexes. Here we report on the NMR solution structure of a G-quadruplex formed by the CEB1 DNA G-rich fragment d(AGGGGGGAGGGAGGGTGG), harboring several G-tracts including one with six continuous guanines. This sequence forms a dimeric G-quadruplex involving the stacking of two subunits, each being a unique snapback parallel-stranded scaffold with three G-tetrad layers, three double-chain-reversal loops, and a V-shaped loop. The two subunits are stacked at their S'-end tetrads, and multiple stacking rotamers may be present due to a high symmetry at the stacking interface. There is a conformational exchange in the millisecond time scale involving a swapping motion between two bases of the six-guanine tract. Our results not only add to the understanding of how the,G-quadruplex formation in human minisatellite leads to genetic instability but also address the fundamental questions regarding stacking of G-quadruplexes and how a long continuous G-tract participates in the structure and conformational dynamics of G-quadruplexes.