State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
Nat Nanotechnol. 2017 Jul;12(6):551-556. doi: 10.1038/nnano.2017.42. Epub 2017 Mar 27.
Hierarchical assemblies of biomolecular subunits can carry out versatile tasks at the cellular level with remarkable spatial and temporal precision. As an example, the collective motion and mutual cooperation between complex protein machines mediate essential functions for life, such as replication, synthesis, degradation, repair and transport. Nucleic acid molecules are far less dynamic than proteins and need to bind to specific proteins to form hierarchical structures. The simplest example of these nucleic acid-based structures is provided by a rod-shaped tobacco mosaic virus, which consists of genetic material surrounded by coat proteins. Inspired by the complexity and hierarchical assembly of viruses, a great deal of effort has been devoted to design similarly constructed artificial viruses. However, such a wrapping approach makes nucleic acid dynamics insensitive to environmental changes. This limitation generally restricts, for example, the amplification of the conformational dynamics between the right-handed B form to the left-handed Z form of double-stranded deoxyribonucleic acid (DNA). Here we report a virus-like hierarchical assembly in which the native DNA and a synthetic coat undergo repeated collective helicity switching triggered by pH change under physiological conditions. We also show that this collective helicity inversion occurs during translocation of the DNA-coat assembly into intracellular compartments. Translating DNA conformational dynamics into a higher level of hierarchical dynamics may provide an approach to create DNA-based nanomachines.
生物分子亚基的层次组装可以在细胞水平上执行多种任务，具有显著的时空精度。例如，复杂蛋白质机器之间的集体运动和相互协作介导了生命的基本功能，如复制、合成、降解、修复和运输。核酸分子的动态性远不及蛋白质，需要与特定的蛋白质结合才能形成层次结构。这些基于核酸的结构最简单的例子是杆状烟草花叶病毒，它由周围包裹着外壳蛋白的遗传物质组成。受病毒复杂性和层次组装的启发，人们投入了大量精力来设计类似结构的人工病毒。然而，这种包裹方法使得核酸的动力学对环境变化不敏感。例如，这种限制通常限制了双链脱氧核糖核酸（DNA）从右手 B 型到左手 Z 型的构象动力学的扩增。在这里，我们报告了一种类似病毒的层次组装，其中天然 DNA 和合成外壳在生理条件下通过 pH 值变化触发的重复集体螺旋转变。我们还表明，这种集体螺旋反转发生在 DNA-外壳组装进入细胞内隔室的转位过程中。将 DNA 构象动力学转化为更高层次的动力学可能为创建基于 DNA 的纳米机器提供一种方法。
