Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.
Nature. 2024 Jul;631(8022):850-856. doi: 10.1038/s41586-024-07616-5. Epub 2024 Jul 17.
Several immune pathways in humans conjugate ubiquitin-like proteins to virus and host molecules as a means of antiviral defence. Here we studied an antiphage defence system in bacteria, comprising a ubiquitin-like protein, ubiquitin-conjugating enzymes E1 and E2, and a deubiquitinase. We show that during phage infection, this system specifically conjugates the ubiquitin-like protein to the phage central tail fibre, a protein at the tip of the tail that is essential for tail assembly as well as for recognition of the target host receptor. Following infection, cells encoding this defence system release a mixture of partially assembled, tailless phage particles and fully assembled phages in which the central tail fibre is obstructed by the covalently attached ubiquitin-like protein. These phages show severely impaired infectivity, explaining how the defence system protects the bacterial population from the spread of phage infection. Our findings demonstrate that conjugation of ubiquitin-like proteins is an antiviral strategy conserved across the tree of life.
在人类中，有几种免疫途径将泛素样蛋白与病毒和宿主分子结合，作为抗病毒防御的一种手段。在这里，我们研究了细菌中的一种抗噬菌体防御系统，该系统包括一种泛素样蛋白、泛素连接酶 E1 和 E2 以及一种去泛素化酶。我们表明，在噬菌体感染期间，该系统特异性地将泛素样蛋白与噬菌体的中央尾部纤维结合，尾部纤维是尾部的顶端蛋白，对于尾部组装以及识别靶宿主受体至关重要。感染后，编码该防御系统的细胞释放出部分组装的、无尾噬菌体颗粒和完全组装的噬菌体的混合物，其中中央尾部纤维被共价连接的泛素样蛋白所阻碍。这些噬菌体的感染性严重受损，解释了防御系统如何保护细菌群体免受噬菌体感染的传播。我们的发现表明，泛素样蛋白的缀合是一种跨生命之树保守的抗病毒策略。
