G-quadruplex conformation and dynamics are determined by loop length and sequence.
G-quadruplex conformation and dynamics are determined by loop length and sequence.
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DOI：
10.1093/nar/gku464
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Myong S
中科院分区：
文献类型：
--
作者：
Tippana R;Xiao W;Myong S
形成富含 G 的四链体序列在整个人类基因组中分布不均匀。它们富含致癌启动子和端粒，引起了人们对靶向 G-四链体 (GQ) 进行抗癌治疗的兴趣。在这里，我们对单分子荧光测量的 GQ 形成序列的构象和动力学进行了定量分析。此外，我们将这些特性与 GQ 靶向配体和 G4 解离酶 1 (G4R1) 蛋白结合联系起来。我们的结果表明，环（非 G 成分）长度和序列都对 GQ 的构象有贡献。实时单分子痕迹表明折叠动力学也取决于环组成。我们证明了 GQ 稳定小分子 N-甲基中卟啉 IX (NMM)、其类似物 NMP 和 G4R1 蛋白选择性地与平行的 GQ 构象结合。我们的研究结果指出了由环长度和序列控制的 GQ 折叠的复杂性，以及 GQ 构象如何决定小分子和蛋白质结合倾向。
The quadruplex forming G-rich sequences are unevenly distributed throughout the human genome. Their enrichment in oncogenic promoters and telomeres has generated interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we present a quantitative analysis on the conformations and dynamics of GQ forming sequences measured by single molecule fluorescence. Additionally, we relate these properties to GQ targeting ligands and G4 resolvase 1 (G4R1) protein binding. Our result shows that both the loop (non-G components) length and sequence contribute to the conformation of the GQ. Real time single molecule traces reveal that the folding dynamics also depend on the loop composition. We demonstrate that GQ-stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and the G4R1 protein bind selectively to the parallel GQ conformation. Our findings point to the complexity of GQ folding governed by the loop length and sequence and how the GQ conformation determines the small molecule and protein binding propensity.
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DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Dhakal S;Cui Y;Koirala D;Ghimire C;Kushwaha S;Yu Z;Yangyuoru PM;Mao H
通讯作者：
Mao H
影响因子：
15
作者：
Dai, Jixun;Carver, Megan;Hurley, Laurence H.;Yang, Danzhou
通讯作者：
Yang, Danzhou
影响因子：
16.8
作者：
Besnard, Emilie;Babied, Amelie;Lemaitre, Jean-Marc
通讯作者：
Lemaitre, Jean-Marc
影响因子：
15
作者：
Jena, Prakrit V.;Shirude, Pravin S.;Okumus, Burak;Laxmi-Reddy, Katta;Godde, Frederic;Huc, Ivan;Balasubramanian, Shankar;Ha, Taekjip
通讯作者：
Ha, Taekjip