The crystal structure of an antiparallel chair-type G-quadruplex formed by Bromo-substituted human telomeric DNA
The crystal structure of an antiparallel chair-type G-quadruplex formed by Bromo-substituted human telomeric DNA
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溴代人端粒 DNA 形成的反平行椅型 G-四链体的晶体结构
DOI：
10.1093/nar/gkz221
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发表时间：
2019-06-04
影响因子：
14.9
通讯作者：
Zhu, Guang
中科院分区：
文献类型：
--
作者：
Geng, Yanyan;Liu, Changdong;Zhu, Guang
摘要人类端粒富含鸟嘌呤的DNA可以采用不同的G-四链结构，在保护细胞免受重组和降解方面发挥着重要作用。尽管这些结构中的许多已经确定，但椅型G-四链结构仍然难以捉摸。在这里，我们提出了一种由人端粒序列d[GGGTTAGG8GTTAGGGTTAGGTTAGG20G]组成的G-四链体的晶体结构，在K+溶液中，在第8位和第20位有两个dG到8br-dG取代，具有syn构象。它形成了具有两个连接三核苷酸环的新型三层椅型G-四链体。特别是，T5和T17通过配位的K+离子和A6·A18碱基对与两个水分子共面，以三明治的方式堆积在G-四元体层上。而扭曲的Hoogsteen A12·T10碱基对则覆盖在G-四分体核心的顶部。三个连接的TTA环是沿边缘方向的，并且每条DNA链具有两条反平行的相邻链。我们的发现有助于更深入地理解和突出环和水分子在G-四链折叠中的独特作用。
Abstract Human telomeric guanine-rich DNA, which could adopt different G-quadruplex structures, plays important roles in protecting the cell from recombination and degradation. Although many of these structures were determined, the chair-type G-quadruplex structure remains elusive. Here, we present a crystal structure of the G-quadruplex composed of the human telomeric sequence d[GGGTTAGG8GTTAGGGTTAGG20G] with two dG to 8Br-dG substitutions at positions 8 and 20 with syn conformation in the K+ solution. It forms a novel three-layer chair-type G-quadruplex with two linking trinucleotide loops. Particularly, T5 and T17 are coplanar with two water molecules stacking on the G-tetrad layer in a sandwich-like mode through a coordinating K+ ion and an A6•A18 base pair. While a twisted Hoogsteen A12•T10 base pair caps on the top of G-tetrad core. The three linking TTA loops are edgewise and each DNA strand has two antiparallel adjacent strands. Our findings contribute to a deeper understanding and highlight the unique roles of loop and water molecule in the folding of the G-quadruplex.