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Folding and structural polymorphism of G-quadruplex formed from a long telomeric sequence containing six GGG tracts

机译:由包含六个GGG片段的长端粒序列形成的G-四链体的折叠和结构多态性

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The structure and stability of a G-quadruplex formed by a long human telomeric sequence containing five or more TTAGGG repeats are not clear yet. Using the guanine-to-inosine (G-to-I) substitution, we conducted thermodynamic studies on the structural polymorphisms of G-quadruplexes formed by the long telomeric sequences, 37htel and five G-to-I substituted sequences (I-1/2, I-1/6, I-4/5, I-4/6, and I-5/6), and investigated their folding dynamics at single-molecule level. The thermodynamic study reveals that a G-quadruplex formed from I-1/2 has a higher T-m and a larger Delta G(298K) than those formed by other G-to-I substituted sequences, suggesting that a long telomeric sequence preferentially forms a thermodynamically stable G-quadruplex at the 3' end. In addition, from changes in the hydrodynamic radius by the formation of a G-quadruplex at single-molecule level, we found that the folding reaction of 37htel may proceed through a two-state mechanism without any detectable intermediate and that the global structure, which leads to the change in molecular size, is still occurring even after the formation of a secondary structure (G-quadruplex).
机译:尚不清楚由包含五个或更多个TTAGGG重复序列的长端粒序列形成的G四联体的结构和稳定性。我们使用鸟嘌呤-肌苷(G-to-I)取代,对由长端粒序列,37htel和五个G-to-I取代序列(I-1 /形成的G-四链体的结构多态性进行了热力学研究。 2,I-1 / 6,I-4 / 5,I-4 / 6和I-5 / 6),并研究了它们在单分子水平上的折叠动力学。热力学研究表明,由I-1 / 2形成的G-四链体比由其他G-to-I取代序列形成的G-四链体具有更高的Tm和更大的Delta G(298K),这表明长端粒序列优先形成一个在3'端具有热力学稳定的G四联体。另外,从在单分子水平上形成G-四链体的流体动力学半径的变化,我们发现37htel的折叠反应可能是通过两态机制进行的,没有任何可检测的中间体,并且整体结构导致分子大小的变化,甚至在形成二级结构(G-四链体)后仍然发生。

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