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Modular Protein Cages for Size-Selective RNA Packaging in Vivo
Journal of the American Chemical Society ( IF 15.0 ) Pub Date : 2018-01-03 , DOI: 10.1021/jacs.7b10798
Yusuke Azuma 1 , Thomas G. W. Edwardson 1 , Naohiro Terasaka 1 , Donald Hilvert 1
Affiliation  

Protein cages have recently emerged as an important platform for nanotechnology development. Of the naturally existing protein cages, viruses are among the most efficient nanomachines, overcoming various barriers to achieve component replication and efficient self-assembly in complex biological milieu. We have designed an artificial system that can carry out the most basic steps of viral particle assembly in vivo. Our strategy is based on patchwork capsids formed from Aquifex aeolicus lumazine synthase and a circularly permuted variant with appended cationic peptides. These two-component protein containers self-assemble in vivo, capturing endogenous RNA molecules in a size-selective manner. By varying the number and design of the RNA-binding peptides displayed on the lumenal surface, the length of guest RNA can be further controlled. Using a fluorescent aptamer, we also show that short-lived RNA species are captured by the protein cage. This platform has potential as a model system for investigating virus assembly, as well as developing RNA regulation or sampling tools to augment biotechnology.

中文翻译:

用于体内尺寸​​选择性 RNA 包装的模块化蛋白质笼

蛋白质笼最近已成为纳米技术发展的重要平台。在天然存在的蛋白质笼中,病毒是最有效的纳米机器之一,它克服了各种障碍,在复杂的生物环境中实现组件复制和高效自组装。我们设计了一个人工系统,可以在体内进行病毒颗粒组装的最基本步骤。我们的策略基于由 Aquifex aeolicus lumazine 合酶和带有附加阳离子肽的循环排列变体形成的拼凑衣壳。这些双组分蛋白质容器在体内自组装,以大小选择性的方式捕获内源性 RNA 分子。通过改变管腔表面展示的 RNA 结合肽的数量和设计,可以进一步控制客体 RNA 的长度。使用荧光适体,我们还表明短寿命的 RNA 物种被蛋白质笼捕获。该平台具有作为研究病毒组装以及开发 RNA 调节或采样工具以增强生物技术的模型系统的潜力。
更新日期:2018-01-03
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