The G-Triplex DNA
The G-Triplex DNA
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DOI：
10.1002/anie.201206522
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Parrinello, Michele
中科院分区：
文献类型：
--
作者：
Limongelli, Vittorio;De Tito, Stefano;Parrinello, Michele
核酸代表细胞语言的字母表，并通过它们的序列和拓扑结构调节重要的细胞功能。近年来，人们发现沃森-克里克双相结构[1]的许多变异在许多细胞过程中起着关键作用。例如发夹、[2]十字链、[3]平行链双链、[4]三链、[5]g -四链、[6]和i-motif这些结构可以由分布在整个人类基因组中的核苷酸序列形成，它们的位置不是随机的，通常与人类疾病有关这些配合物由一到四股形成，通过碱基堆叠和氢键相互作用稳定，具有各种非标准配对。例如，DNA三联体可以出现G: GC、A: AT、C+: GC和T: AT配对，其中两条链为标准的沃森-克里克双链结构（即GC和AT），第三条链位于双链的主槽中。相比之下，g -四聚体是通过两个或多个鸟嘌呤四聚体的堆叠来稳定的四链结构（图1）。这些例子突出了DNA的结构多态性，并表明可能存在其他结构，可能具有迄今为止未知的特定细胞功能。在此，利用元动力学模拟，我们鉴定了凝血酶结合适体（TBA）四联体的一个稳定的折叠中间体这种中间体的特征是“G-三聚体”结构，具有G: G: G三聚体平面，由一组胡格斯汀式氢键稳定（图1）。这种结构已经在其他理论中得到了假设
Nucleic acids represent the alphabet of the cellular language and through their sequence and topology regulate vital cellular functions. In recent years, it has been found that many variations from the Watson–Crick duplex structure [1] play key roles in many cellular processes. Examples are hairpins,[2] cruciforms,[3] parallel-stranded duplexes,[4] triplexes,[5] G-quadruplexes,[6] and the i-motif.[7] These structures can be formed by nucleotide sequences distributed throughout the whole human genome, their location is not random and often associated with human diseases.[8] These complexes are formed from one to four strands, stabilized by base stacking and hydrogen bond interactions, with a variety of non-standard pairings. For instance, DNA triplexes can present G: GC, A: AT, C+: GC, and T: AT pairings, with two strands in the standard Watson–Crick duplex structure (ie GC and AT) and the third one lying in the major groove of the duplex. In contrast, G-quadruplexes are four-stranded structures stabilized by stacking of two or more guanine tetrads (Figure 1).These examples highlight the structural polymorphism of DNA and suggest that other structures might exist, perhaps with specific cellular functions that are, to date, unknown. Herein, using metadynamics simulations,[9] we have identified a stable folding intermediate of the thrombin binding aptamer (TBA) quadruplex.[10] This intermediate is characterized by a “G-triplex” structure, having G: G: G triad planes stabilized by an array of Hoogsteen-like hydrogen-bonds (Figure 1). This kind of structure has been already hypothesized in other