Coexistence of Two Distinct G-Quadruplex Conformations in the hTERT Promoter
Coexistence of Two Distinct G-Quadruplex Conformations in the hTERT Promoter
复制标题
DOI：
10.1021/ja101252n
复制
发表时间：
2010-09-08
影响因子：
15
通讯作者：
Phan, Anh Tuan
中科院分区：
文献类型：
--
作者：
Lim, Kah Wai;Lacroix, Laurent;Phan, Anh Tuan
在大多数癌细胞中，人端粒酶的催化亚基hTERT活跃地延长端粒的3'末端。hTERT启动子在同一条DNA链上含有许多富含鸟嘌呤的片段，具有形成G-四链体的特殊潜力。在这里，我们表明，一个特定的G-丰富的序列在这一地区共存于两个G-四链体构象在钾溶液中：（3 + 1）和平行链的G-四链体。我们提出了两种构象的NMR溶液结构，每个构象都包含几个强大的结构元素，其中包括（3 + 1）和所有平行的G-四分体核心，单残基双链反转环，和一个帽A.T碱基对。结合NMR和CD技术，辅以序列修改和实验条件的变化，使我们能够更好地了解两种G-四链体构象在平衡状态下的共存，以及不同的结构元素如何共同支持特定的形式。
The catalytic subunit of human telomerase, hTERT, actively elongates the 3' end of the telomere in most cancer cells. The hTERT promoter, which contains many guanine-rich stretches on the same DNA strand, exhibits an exceptional potential for G-quadruplex formation. Here we show that one particular G-rich sequence in this region coexists in two G-quadruplex conformations in potassium solution: a (3 + 1) and a parallel-stranded G-quadruplexes. We present the NMR solution structures of both conformations, each comprising several robust structural elements, among which include the (3 + 1) and all-parallel G-tetrad cores, single-residue double-chain-reversal loops, and a capping A.T base pair. A combination of NMR and CD techniques, complemented with sequence modifications and variations of experimental condition, allowed us to better understand the coexistence of the two G-quadruplex conformations in equilibrium and how different structural elements conspire to favor a particular form.