不同G-四链体之间的再组装

Reassembly between two distinct G-quadruplexes

主要通过液体核磁共振等技术发现,凝血酶适配体的突变序列TBA-M、人源端粒序列htel3在Na^(+)溶液中可各自折叠成G-四链体结构,而这两个预先已折叠完好的G-四链体之间还能够自发地通过DNA链置换作用再进一步重新组装成异分子间G-四链体复合物TBA-M/htel3。该复合物中,TBA-M与htel3之间相互结合的DNA链当量比为1∶1,并且TBA-M仅以其3′末端3个连续鸟嘌呤残基(G_(14)G_(15)G_(16))参与TBA-M/htel3复合物中G-四链体核心区的Hoogsteen氢键配对。首次通过实验证明已经预先形成结构的两个G-四链体之间还能够进一步发生基于Hoogsteen氢键配对的DNA链置换现象,并且对其相互作用的过程与分子机制进行探讨。拓展对不同核酸结构之间相互作用方式与识别机制的更深层认知。

Here,mainly through solution NMR experiments,we found that the mutant sequence of Thrombin Binding Aptamer(TBA-M)and human telomeric sequence htel3 self-fold into G-quadruplexes in sodium solution,respectively.Appealingly,these two well pre-folded G-quadruplexes can further reassemble into a new heteromolecular G-quadruplex complex(TBA-M/htel3)spontaneously through DNA strand displacement.The stoichiometric ratio between TBA-M and htel3 in the complex is identified as 1∶1.The last three guanosines(G_(14)G_(15)G_(16))from the 3′-end of TBA-M are involved in the formation of the G-quadruplex core of TBA-M/htel3 complex via Hoogsteen base pairing.In this paper,we reveal for the first time that two well pre-folded G-quadruplexes enable a further Hoogsteen pairing-based DNA strand displacement,in which the reaction process and molecular mechanism are also investigated primarily.Our finding expands the understanding of the interacting pattern and recognition mechanism between differently folded structures of nucleic acids.