Molecular mechanism of bacteriophage tail contraction-structure of an S-layer-penetrating bacteriophage
Molecular mechanism of bacteriophage tail contraction-structure of an S-layer-penetrating bacteriophage
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噬菌体尾部收缩的分子机制-S层穿透噬菌体的结构
DOI：
10.1101/2023.08.04.551987
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Wilson J
中科院分区：
文献类型：
--
作者：
Wilson J
感染细菌的病毒（噬菌体或噬菌体）附着在宿主细胞包膜上，将其遗传物质注入宿主细胞质中，并作为原噬菌体或劫持宿主机器以产生后代病毒体。附着通过对不同宿主细胞表面分子特异性的噬菌体受体结合蛋白介导。噬菌体的一个子集，肌病毒，具有可收缩的尾巴，其外鞘在受体结合时收缩，驱动内尾管穿过细胞包膜并将噬菌体基因组递送到宿主细胞质中。噬菌体尾部收缩的分子细节和细胞包膜穿透的模式仍然知之甚少，并且对于任何被蛋白质S层包裹的噬菌体感染细菌是完全未知的。在这里，我们揭示了一个完整的收缩尾噬菌体的延伸和收缩的原子结构，结合并穿透革兰氏阳性人类病原体艰难梭菌的保护性S层。令人惊讶的是，我们发现没有证据的内在的酶结构域，其他酶利用细胞壁渗透，这表明，足够的能量后释放尾部收缩穿透S-层和厚的细胞壁没有酶活性。然而，还值得注意的是，尾鞘亚基的移动比在相关的收缩注射系统，如模型噬菌体T4中研究的那些少。相反，异常长的尾部长度和收缩时的柔性可能有助于实现包封穿透所需的自由能释放。我们的研究结果表明，噬菌体收缩和感染的原则，确定在模型系统的T4是不普遍的。我们预计我们的结构将形成一个强大的基础engineerC。艰难梭菌作为治疗剂，并强调为了感染含有病原体的S层而进行的重要适应。
Viruses that infect bacteria (bacteriophages or phages) attach to the host cell envelope, inject their genetic material into the host cytosol and either persist as prophage or hijack the host machinery to produce progeny virions. Attachment is mediated through phage receptor binding proteins that are specific for different host cell surface molecules. A subset of phage, the myoviruses, possess contractile tails, the outer sheath of which contracts upon receptor binding, driving an inner tail tube through the cell envelope and delivering the phage genome into the host cytosol. The molecular details of phage tail contraction and mode of cell envelope penetration have remained poorly understood and were completely unknown for any phage infecting bacteria enveloped by a proteinaceous S-layer. Here we reveal the extended and contracted atomic structures of an intact contractile-tail phage that binds to and penetrates the protective S-layer of the Gram positive human pathogenClostridioides difficile. Surprisingly, we find no evidence of the intrinsic enzymatic domains that other phages exploit in cell wall penetration, suggesting that sufficient energy is released upon tail contraction to penetrate the S-layer and the thick cell wall without enzymatic activity. However, it is also notable that the tail sheath subunits move less than those studied in related contractile injection systems such as the model phage T4. Instead, the unusually long tail length and flexibility upon contraction likely contribute towards the required free energy release for envelope penetration. Our results show that the principles of phage contraction and infection as determined in the model system of T4 are not universal. We anticipate that our structures will form a strong foundation to engineerC. difficilephages as therapeutics, and highlight important adaptations made in order to infect S-layer containing pathogens.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
3.7
作者：
Whittle MJ;Bilverstone TW;van Esveld RJ;Lücke AC;Lister MM;Kuehne SA;Minton NP
通讯作者：
Minton NP
影响因子：
3.7
作者：
通讯作者：
--
影响因子：
3.2
作者：
Gebhart, Dana;Williams, Steven R.;Scholl, Dean
通讯作者：
Scholl, Dean
DOI：
10.1107/s2059798315021142
发表时间：
2016-01-01
影响因子：
2.2
作者：
Spinola-Amilibia, Mercedes;Davo-Siguero, Irene;Romero, Antonio
通讯作者：
Romero, Antonio