Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia; EN-FIST Center of Excellence, SI-1000, Ljubljana, Slovenia; Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000, Ljubljana, Slovenia.
Biochimie. 2023 Nov;214(Pt A):73-82. doi: 10.1016/j.biochi.2023.08.002. Epub 2023 Aug 10.
The human telomere oligonucleotide, d[TAGGG(TTAGGG)TTAGG] (TAGGG), can adopt two distinct 2-G-quartet G-quadruplex structures at pH 7.0 and 5.0, referred to as the TD and KDH forms, respectively. By using a combination of NMR and computational techniques, we determined high-resolution structures of both forms, which revealed unique loop architectures, base triples, and base pairs that play a crucial role in the pH-driven structural transformation of TAGGG. Our study demonstrated that TAGGG represents a reversible pH-driven switch system where the stability and pH-induced structural transformation of the G-quadruplexes are influenced by the terminal residues and base triples. Gaining insight into the factors that regulate the formation of G-quadruplexes and their pH-sensitive structural equilibrium holds great potential for the rational design of novel DNA based pH-driven switches. These advancements in understanding create exciting opportunities for applications in the field of nanotechnology, specifically in the development of bio-nano-motors.
人端粒寡核苷酸 d[TAGGG(TTAGGG)TTAGG]（TAGGG）在 pH 值为 7.0 和 5.0 时可以分别采取两种不同的 2-G-四联体 G-四链体结构，分别称为 TD 和 KDH 形式。通过结合使用 NMR 和计算技术，我们确定了这两种形式的高分辨率结构，揭示了独特的环结构、碱基三对和碱基对，这些在 TAGGG 的 pH 驱动结构转变中起着关键作用。我们的研究表明，TAGGG 代表了一种可逆的 pH 驱动开关系统，其中 G-四链体的稳定性和 pH 诱导的结构转变受末端残基和碱基三对的影响。深入了解调节 G-四链体形成及其 pH 敏感结构平衡的因素，为合理设计基于 DNA 的新型 pH 驱动开关提供了巨大的潜力。这些对理解的深入研究为纳米技术领域的应用，特别是在生物纳米马达的开发方面，创造了令人兴奋的机会。
