Institute of Organic Chemistry and Biochemistry ASCR , Prague 166 10 , Czech Republic.
Department of Biochemistry and Microbiology , University of Chemistry and Technology , Prague 166 28 , Czech Republic.
ACS Chem Biol. 2019 Sep 20;14(9):1951-1963. doi: 10.1021/acschembio.9b00428. Epub 2019 Sep 5.
G-Quadruplexes are noncanonical nucleic acid structures made up of stacked guanosine tetrads connected by short loops. They are frequently used building blocks in synthetic biology and thought to play widespread biological roles. Multimerization can change the functional properties of G-quadruplexes, and understanding the factors that modulate this process remains an important goal. Here, we report the discovery of a novel mechanism by which the formation of multimeric G-quadruplexes can be controlled using GTP. We show that GTP likely inhibits multimer formation by becoming incorporated into a tetrad in the monomeric form of the structure and define the sequence requirements of G-quadruplexes that form GTP-dependent structures. These experiments provide new insights into the small molecule control of G-quadruplex multimerization. They also suggest possible roles for GTP-dependent multimeric G-quadruplexes in both synthetic and natural biological systems.
四链体是由短环连接的堆叠鸟苷四联体组成的非规范核酸结构。它们是合成生物学中常用的构建模块，被认为在广泛的生物学中发挥作用。多聚化可以改变四链体的功能特性，了解调节这一过程的因素仍然是一个重要目标。在这里，我们报告了一种新的机制的发现，即使用 GTP 控制多聚体四链体的形成。我们表明，GTP 可能通过在结构的单体形式中掺入四联体来抑制多聚体的形成，并定义形成 GTP 依赖性结构的四链体的序列要求。这些实验为小分子控制四链体多聚化提供了新的见解。它们还表明 GTP 依赖性多聚体四链体在合成和天然生物系统中可能发挥作用。
