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DOI | 10.1126/science.abg2822 |
Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein | |
Stephan Tetter; Naohiro Terasaka; Angela Steinauer; Richard J. Bingham; Sam Clark; Andrew J. P. Scott; Nikesh Patel; Marc Leibundgut; Emma Wroblewski; Nenad Ban; Peter G. Stockley; Reidun Twarock; Donald Hilvert | |
2021-06-11 | |
发表期刊 | Science |
出版年 | 2021 |
英文摘要 | Artificial nucleocapsid proteins, which could be analogous to those used by viruses to package their genomes, are a promising way to protect and deliver RNAs. Using an escalating challenge by nucleases, Tetter et al. evolved a protein that forms multimeric, spherical cages into a highly efficient capsid that selectively packages its own encoding RNA. Cryo–electron microscopy of the final design and intermediates revealed a stepwise expansion in size, enabled by destabilizing amino acid substitutions and a domain swap that results in a change of oligomerization interfaces for the base units of the cage. In addition to altering the protein, directed evolution resulted in changes to the encoding RNA structure that enabled efficient uptake versus other cellular RNAs. Science , abg2822, this issue p. [1220][1] Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity. In addition to evincing a plausible evolutionary pathway for primordial viruses, these findings highlight practical strategies for developing nonviral carriers for diverse vaccine and delivery applications. [1]: /lookup/doi/10.1126/science.abg2822 |
领域 | 气候变化 ; 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/329918 |
专题 | 气候变化 资源环境科学 |
推荐引用方式 GB/T 7714 | Stephan Tetter,Naohiro Terasaka,Angela Steinauer,et al. Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein[J]. Science,2021. |
APA | Stephan Tetter.,Naohiro Terasaka.,Angela Steinauer.,Richard J. Bingham.,Sam Clark.,...&Donald Hilvert.(2021).Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein.Science. |
MLA | Stephan Tetter,et al."Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein".Science (2021). |
条目包含的文件 | 条目无相关文件。 |
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