School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
Centre for Molecular and Structural Biochemistry, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
Nucleic Acids Res. 2018 Jul 6;46(12):5886-5893. doi: 10.1093/nar/gky390.
Previous computational studies have shown that Cu+ can act as a substitute for H+ to support formation of cytosine (C) dimers with similar conformation to the hemi-protonated base pair found in i-motif DNA. Through a range of biophysical methods, we provide experimental evidence to support the hypothesis that Cu+ can mediate C-C base pairing in i-motif DNA and preserve i-motif structure. These effects can be reversed using a metal chelator, or exposure to ambient oxygen in the air that drives oxidation of Cu+ to Cu2+, a comparatively weak ligand. Herein, we present a dynamic and redox-sensitive system for conformational control of an i-motif forming DNA sequence in response to copper cations.
先前的计算研究表明，Cu+可以替代 H+，支持胞嘧啶（C）二聚体的形成，其构象与 i 型 DNA 中半质子化的碱基对相似。通过一系列生物物理方法，我们提供了实验证据来支持 Cu+可以介导 i 型 DNA 中的 C-C 碱基配对并维持 i 型结构的假设。这些效应可以通过金属螯合剂或暴露于空气中的环境氧气来逆转，后者会将 Cu+氧化为 Cu2+，Cu2+是一种相对较弱的配体。在此，我们提出了一个动态的和氧化还原敏感的系统，用于响应铜阳离子对 i 型形成 DNA 序列的构象控制。
