Molecular Modeling and Simulation Group, National Institutes for Quantum and Radiological Science and Technology, 8-1-7 Umemidai, Kizugawa 619-0215, Japan.
Research Reactor Institute, Kyoto University, 2 Asashironishi, Kumatori, Osaka 590-0494, Japan.
Acta Crystallogr D Struct Biol. 2017 Jul 1;73(Pt 7):600-608. doi: 10.1107/S2059798317007707. Epub 2017 Jun 22.
Conformational flexibility of DNA plays important roles in biological processes such as transcriptional regulation and DNA packaging etc. To understand the mechanisms of these processes, it is important to analyse when, where and how DNA shows conformational variations. Recent analyses have indicated that conventional refinement methods do not always provide accurate models of crystallographic heterogeneities and that some information on polymorphism has been overlooked in previous crystallographic studies. In the present study, the m|F| - D|F| electron-density maps of double-helical DNA crystal structures were calculated at a resolution equal to or better than 1.5 Å and potential conformational transitions were found in 27% of DNA phosphates. Detailed analyses of the m|F| - D|F| peaks indicated that some of these unassigned densities correspond to ZI ↔ ZII or A/B → BI conformational transitions. A relationship was also found between ZI/ZII transitions and metal coordination in Z-DNA from the detected peaks. The present study highlights that frequent transitions of phosphate backbones occur even in crystals and that some of these transitions are affected by the local molecular environment.
DNA 的构象灵活性在转录调控和 DNA 包装等生物过程中发挥着重要作用。为了理解这些过程的机制，分析 DNA 在何时、何地以及如何发生构象变化是很重要的。最近的分析表明，传统的精修方法并不总是能提供晶体异质结构的准确模型，而且在以前的晶体学研究中，有些关于多态性的信息被忽视了。在本研究中，我们计算了分辨率等于或优于 1.5 Å 的双链 DNA 晶体结构的 m|F| - D|F| 电子密度图，发现 27%的 DNA 磷酸基存在潜在的构象转变。对 m|F| - D|F| 峰的详细分析表明，其中一些未分配的密度对应于 ZI↔ZII 或 A/B→BI 构象转变。从检测到的峰中还发现了 ZI/ZII 转变与 Z-DNA 中金属配位之间的关系。本研究强调了即使在晶体中，磷酸骨架也会频繁发生转变，而且其中一些转变受到局部分子环境的影响。
