Adenine-Driven Structural Switch from a Two- to Three-Quartet DNA G-Quadruplex.,Angewandte Chemie International Edition

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Adenine-Driven Structural Switch from a Two- to Three-Quartet DNA G-Quadruplex.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2018-10-17 , DOI: 10.1002/anie.201809328
Martina Lenarčič Živković ₁ , Jan Rozman ₁ , Janez Plavec _{1,

2,

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Affiliation

A G-rich sequence found in the regulatory region of the RANKL gene, which is associated with homeostasis of bone metabolism, folds into a two-quartet basket-type G-quadruplex stabilized by A⋅G⋅A and G⋅G⋅G base-triads. Perusal of local structural features together with G/A-to-T modifications uncovered the critical role of A5 for the formation of a distinct antiparallel two-quartet topology and not the three-quartet topology that would be expected based on the sequence with four GGG-tracts alone. The structural changes induced by the A5-to-T5 modification include a switch in orientation and relative positions of G-strands that together with anti to syn reorientation of G12 provide insights into the complexity of the interactions that influence the folding of G-rich DNA. Understanding the impact of loop residues on the stability and formation of G-quadruplexes advances our knowledge and ability to predict structures adopted by G-rich sequences, which are involved in regulatory mechanisms in the cell, and may also facilitate drug design.

中文翻译：

腺嘌呤驱动的从二四重体 DNA G 四联体到三四重体 DNA G 四联体的结构转换。

在 RANKL 基因调控区发现的富含 G 的序列与骨代谢稳态相关，折叠成由 A⋅G⋅A 和 G⋅G⋅G 碱基稳定的两个四重体篮式 G 四链体-三合会。仔细研究局部结构特征以及 G/A 到 T 的修饰，揭示了 A5 对于形成独特的反平行二四重奏拓扑而不是基于具有四个 GGG 的序列所预期的三四重奏拓扑的关键作用-单独的小册子。 A5 至 T5 修饰引起的结构变化包括 G 链方向和相对位置的转换，再加上 G12 的反向顺式重新定向，可以深入了解影响富含 G 的 DNA 折叠的相互作用的复杂性。了解环残基对 G 四链体稳定性和形成的影响提高了我们预测富含 G 序列所采用结构的知识和能力，这些序列参与细胞的调节机制，也可能有助于药物设计。

更新日期：2018-10-17

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