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The bacteriophage phi 29 tail possesses a pore-forming loop for cell membrane penetration

机译:噬菌体phi 29尾部具有成孔环,可穿透细胞膜

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摘要

Most bacteriophages are tailed bacteriophages with an isometric or a prolate head attached to a long contractile, long non-contractile, or short non-contractile tail(1). The tail is a complex machine that plays a central role in host cell recognition and attachment, cell wall and membrane penetration, and viral genome ejection. The mechanisms involved in the penetration of the inner host cell membrane by bacteriophage tails are not well understood. Here we describe structural and functional studies of the bacteriophage phi 29 tail knob protein gene product 9 (gp9). The 2.0 angstrom crystal structure of gp9 shows that six gp9 molecules form a hexameric tube structure with six flexible hydrophobic loops blocking one end of the tube before DNA ejection. Sequence and structural analyses suggest that the loops in the tube could be membrane active. Further biochemical assays and electron microscopy structural analyses show that the six hydrophobic loops in the tube exit upon DNA ejection and form a channel that spans the lipid bilayer of the membrane and allows the release of the bacteriophage genomic DNA, suggesting that cell membrane penetration involves a pore-forming mechanism similar to that of certain non-enveloped eukaryotic viruses(2-4). A search of other phage tail proteins identified similar hydrophobic loops, which indicates that a common mechanism might be used for membrane penetration by prokaryotic viruses. These findings suggest that although prokaryotic and eukaryotic viruses use apparently very different mechanisms for infection, they have evolved similar mechanisms for breaching the cell membrane.
机译:大多数噬菌体是尾巴状的噬菌体,其头部等长或长于长的可收缩,长的非收缩性或短的非收缩性尾巴(1)。尾巴是一台复杂的机器,在宿主细胞识别和附着,细胞壁和膜穿透以及病毒基因组弹出中起着核心作用。噬菌体尾部穿透内部宿主细胞膜的机制尚不清楚。在这里,我们描述了噬菌体phi 29尾突蛋白基因产物9(gp9)的结构和功能研究。 gp9的2.0埃晶体结构表明,六个gp9分子形成六聚管结构,具有六个柔性疏水环,在DNA弹出之前会阻塞管的一端。序列和结构分析表明,试管中的环可能具有膜活性。进一步的生化分析和电子显微镜结构分析表明,DNA弹出时管中的六个疏水环退出,并形成一个跨膜脂质双层的通道,并允许释放噬菌体基因组DNA,这表明细胞膜的渗透涉及与某些非包膜真核病毒相似的成孔机制(2-4)。对其他噬菌体尾部蛋白质的搜索发现了类似的疏水环,这表明原核病毒可能会使用一种常见的机制来穿透膜。这些发现表明,尽管原核和真核病毒使用明显不同的感染机制,但它们已经进化出类似的机制来破坏细胞膜。

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  • 来源
    《Nature》 |2016年第7608期|544-547|共4页
  • 作者单位

    Tsinghua Univ, Ctr Infect Dis Res, Collaborat Innovat Ctr Diag & Treatment Infect Di, Dept Basic Med Sci,Sch Med,Beijing Adv Innovat Ct, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Infect Dis Res, Collaborat Innovat Ctr Diag & Treatment Infect Di, Dept Basic Med Sci,Sch Med,Beijing Adv Innovat Ct, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Infect Dis Res, Collaborat Innovat Ctr Diag & Treatment Infect Di, Dept Basic Med Sci,Sch Med,Beijing Adv Innovat Ct, Beijing 100084, Peoples R China;

    Tsinghua Univ, Ctr Infect Dis Res, Collaborat Innovat Ctr Diag & Treatment Infect Di, Dept Basic Med Sci,Sch Med,Beijing Adv Innovat Ct, Beijing 100084, Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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