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基于细菌的基因分析检测朊病毒形成。

A bacteria-based genetic assay detects prion formation.

机构信息

Department of Microbiology, Blavatnik Institue, Harvard Medical School, Boston, MA 02115.

Department of Microbiology, Blavatnik Institue, Harvard Medical School, Boston, MA 02115

出版信息

Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4605-4610. doi: 10.1073/pnas.1817711116. Epub 2019 Feb 19.

Abstract

Prions are infectious, self-propagating protein aggregates that are notorious for causing devastating neurodegenerative diseases in mammals. Recent evidence supports the existence of prions in bacteria. However, the evaluation of candidate bacterial prion-forming proteins has been hampered by the lack of genetic assays for detecting their conversion to an aggregated prion conformation. Here we describe a bacteriabased genetic assay that distinguishes cells carrying a model yeast prion protein in its nonprion and prion forms. We then use this assay to investigate the prion-forming potential of single-stranded DNA-binding protein (SSB) of Our findings indicate that SSB possesses a prion-forming domain that can transition between nonprion and prion conformations. Furthermore, we show that bacterial cells can propagate the prion form over 100 generations in a manner that depends on the disaggregase ClpB. The bacteria-based genetic tool we present may facilitate the investigation of prion-like phenomena in all domains of life.

摘要

朊病毒是传染性的、自我复制的蛋白质聚集体,以在哺乳动物中引起破坏性的神经退行性疾病而臭名昭著。最近的证据支持朊病毒存在于细菌中。然而,由于缺乏用于检测其转化为聚集朊病毒构象的遗传检测方法,候选细菌朊病毒形成蛋白的评估受到了阻碍。在这里,我们描述了一种基于细菌的遗传检测方法,该方法可区分携带模型酵母朊病毒蛋白的非朊病毒和朊病毒形式的细胞。然后,我们使用该检测方法研究了单链 DNA 结合蛋白 (SSB) 的朊病毒形成潜力。我们的研究结果表明,SSB 具有一个朊病毒形成结构域,可在非朊病毒和朊病毒构象之间转换。此外,我们表明,细菌细胞可以以依赖解聚酶 ClpB 的方式在 100 多代中传播朊病毒形式。我们提出的基于细菌的遗传工具可能有助于研究所有生命领域的朊病毒样现象。

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Molecular basis for diversification of yeast prion strain conformation.酵母朊病毒株构象多样化的分子基础。
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Protein-Based Inheritance: Epigenetics beyond the Chromosome.基于蛋白质的遗传:超越染色体的表观遗传学。
Mol Cell. 2018 Jan 18;69(2):195-202. doi: 10.1016/j.molcel.2017.10.030. Epub 2017 Nov 16.
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A bacterial global regulator forms a prion.一种细菌全局调节因子形成了朊病毒。
Science. 2017 Jan 13;355(6321):198-201. doi: 10.1126/science.aai7776.
7
The tale of SSB.单链结合蛋白的故事。
Prog Biophys Mol Biol. 2017 Aug;127:111-118. doi: 10.1016/j.pbiomolbio.2016.11.001. Epub 2016 Nov 9.
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Cell Biology of Prions and Prionoids: A Status Report.朊病毒和拟朊病毒的细胞生物学:现状报告。
Trends Cell Biol. 2016 Jan;26(1):40-51. doi: 10.1016/j.tcb.2015.08.007. Epub 2015 Oct 9.

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