Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations
Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations
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DOI：
10.1016/j.bpj.2015.05.001
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发表时间：
2015-06-16
影响因子：
3.4
通讯作者：
Lah, Jurij
中科院分区：
文献类型：
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作者：
Boncina, Matjaz;Hamon, Florian;Lah, Jurij
近年来，人们提出了端粒DNA折叠成G-四链体以及配体与这些结构结合的各种途径。然而，驱动折叠和识别过程的力的性质的关键问题仍然没有答案。本文用量热法、光谱法和凝胶电泳法研究了离子（K ~+、Na ~+）与特异性双喹啉配体结合引起的22-mer ht-DNA片段（Tel 22）的结构变化。使用各种各样的实验数据的全局模型分析，我们能够表征的热力学力，支配形成稳定的Tel 22 G-四链体，折叠中间体，和配体-四链体复合物，然后预测Tel 22在水溶液中的行为作为温度，盐浓度和配体浓度的函数。在此基础上，我们认为我们的工作为更好地理解ht-DNA折叠和结合途径的异质性及其结构多态性奠定了基础。
Recently various pathways of human telomere (ht) DNA folding into G-quadruplexes and of ligand binding to these structures have been proposed. However, the key issue as to the nature of forces driving the folding and recognition processes remains unanswered. In this study, structural changes of 22-mer ht-DNA fragment (Tel22), induced by binding of ions (K+, Na+) and specific bisquinolinium ligands, were monitored by calorimetric and spectroscopic methods and by gel electrophoresis. Using the global model analysis of a wide variety of experimental data, we were able to characterize the thermodynamic forces that govern the formation of stable Tel22 G-quadruplexes, folding intermediates, and ligand-quadruplex complexes, and then predict Tel22 behavior in aqueous solutions as a function of temperature, salt concentration, and ligand concentration. On the basis of the above, we believe that our work sets the framework for better understanding the heterogeneity of ht-DNA folding and binding pathways, and its structural polymorphism.