Structure of the human telomere in K+ solution: a stable basket-type G-quadruplex with only two G-tetrad layers.

Structure of the human telomere in K+ solution: a stable basket-type G-quadruplex with only two G-tetrad layers.
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DOI:
10.1021/ja807503g
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发表时间:
2009-04-01
影响因子:
15
通讯作者:
Phan AT
Phan AT
中科院分区:
化学1区
文献类型:
--
作者:
Lim KW;Amrane S;Bouaziz S;Xu W;Mu Y;Patel DJ;Luu KN;Phan AT

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以前,已经报道了人端粒DNA序列在不同的实验条件下可以采用四种不同的分子内G-四链体,每种分子内G-四链体包括三个G-四联体层,即Na+-溶液反平行链篮形式、K+-晶体平行链螺旋桨形式、K+-溶液(3+1)形式1和K+-溶液(3+1)形式2。在这里,我们提出了一个新的分子内G-四链体通过四个重复的人端粒序列在K+溶液(形式3)。这种结构是一个只有两层G-四联体的篮型G-四链体:环依次为边向、对角和边向;每个四联体周围的鸟嘌呤糖苷构象为syn·syn·anti·anti;核心的每条链都有平行和反平行的相邻链;有一个窄槽、一个宽槽和两个中等槽。尽管在核心中仅存在两个G-四联体,但这种结构比先前在K+溶液中观察到的人类端粒序列的三个G-四联体分子内G-四联体更稳定。形式3的详细结构解析揭示了覆盖G-四联体核心两端的环中的广泛碱基配对和堆叠,这可以解释结构的高稳定性。这种新的结构突出了人类端粒DNA的构象异质性。它揭示了G-四链体的新折叠原理,并提出了新的环序列和结构,用于靶向人类端粒DNA。
Previously, it has been reported that human telomeric DNA sequences could adopt in different experimental conditions four different intramolecular G-quadruplexes each involving three G-tetrad layers, namely Na+-solution antiparallel-stranded basket form, K+-crystal parallel-stranded propeller form, K+-solution (3+1) Form 1 and K+-solution (3+1) Form 2. Here we present a new intramolecular G-quadruplex adopted by a four-repeat human telomeric sequence in K+ solution (Form 3). This structure is a basket-type G-quadruplex with only two G-tetrad layers: loops are successively edgewise, diagonal and edgewise; glycosidic conformations of guanines are syn•syn•anti•anti around each tetrad; each strand of the core has both a parallel and an antiparallel adjacent strands; there are one narrow, one wide and two medium grooves. Despite the presence of only two G-tetrads in the core, this structure is more stable than the three-G-tetrad intramolecular G-quadruplexes previously observed for human telomeric sequences in K+ solution. Detailed structural elucidation of Form 3 revealed extensive base pairing and stacking in the loops capping both ends of the G-tetrad core, which might explain the high stability of the structure. This novel structure highlights the conformational heterogeneity of human telomeric DNA. It revealed a new folding principle for G-quadruplexes and suggests new loop sequences and structures for targeting in human telomeric DNA.
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