Bing Tao, Zheng Wei, Zhang Xin, Shen Luyao, Liu Xiangjun, Wang Fuyi, Cui Jie, Cao Zehui, Shangguan Dihua
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Sci Rep. 2017 Nov 13;7(1):15467. doi: 10.1038/s41598-017-15797-5.
Apart from the canonical Watson-Crick duplex, nucleic acids can often form other structures, e.g. G-quadruplex and triplex. These structures give nucleic acid additional functions besides coding for genetic information. Aptamers are one type of functional nucleic acids that bind to specific targets with high selectivity and affinity by folding into special tertiary structures. Despite the fact that numerous aptamers have been reported, only a few different types of aptamer structures are identified. Here we report a novel triplex-quadruplex hybrid scaffold formed by a codeine binding aptamer (CBA). CBA and its derivatives are G-rich DNA sequences. Codeine binding can induce the formation of a complex structure for this aptamer containing a G-quadruplex and a G·GC triplex, while codeine is located at the junction of the triplex and quadruplex. When split CBA into two moieties, codeine does not bind either moieties individually, but can bind them together by inducing the formation of the triplex-quadruplex scaffold. This structure formation induced by codeine binding is shown to inhibit polymerase reaction, which shows a potential application of the aptamer sequence in gene regulations.
除了经典的沃森-克里克双链体,核酸通常还能形成其他结构,例如G-四链体和三链体。这些结构赋予了核酸除编码遗传信息之外的其他功能。适体是一类功能性核酸,通过折叠成特殊的三级结构以高选择性和亲和力与特定靶标结合。尽管已经报道了大量适体,但仅鉴定出少数几种不同类型的适体结构。在此我们报道了一种由可待因结合适体(CBA)形成的新型三链体-四链体杂合支架。CBA及其衍生物是富含G的DNA序列。可待因结合可诱导该适体形成一种包含G-四链体和G·GC三链体的复杂结构,而可待因位于三链体和四链体的交界处。当将CBA拆分成两个部分时,可待因不会分别与任何一个部分结合,但可通过诱导形成三链体-四链体支架将它们结合在一起。由可待因结合诱导的这种结构形成被证明可抑制聚合酶反应,这表明该适体序列在基因调控方面具有潜在应用。