State Key Laboratory of Agricultural Microbiology and College of Life Sciences and Technology, Huazhong Agricultural University, 430070 Wuhan, China; Hubei Hongshan Laboratory, 430070 Wuhan, China.
Section of Microbiology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen, Denmark.
Cell Host Microbe. 2022 Jul 13;30(7):930-943.e6. doi: 10.1016/j.chom.2022.04.015. Epub 2022 May 19.
Argonaute (Ago) proteins are widespread nucleic-acid-guided enzymes that recognize targets through complementary base pairing. Although, in eukaryotes, Agos are involved in RNA silencing, the functions of prokaryotic Agos (pAgos) remain largely unknown. In particular, a clade of truncated and catalytically inactive pAgos (short pAgos) lacks characterization. Here, we reveal that a short pAgo protein in the archaeon Sulfolobus islandicus, together with its two genetically associated proteins, Aga1 and Aga2, provide robust antiviral protection via abortive infection. Aga2 is a toxic transmembrane effector that binds anionic phospholipids via a basic pocket, resulting in membrane depolarization and cell killing. Ago and Aga1 form a stable complex that exhibits nucleic-acid-directed nucleic-acid-recognition ability and directly interacts with Aga2, pointing to an immune sensing mechanism. Together, our results highlight the cooperation between pAgos and their widespread associated proteins, suggesting an uncharted diversity of pAgo-derived immune systems.
Argonaute (Ago) 蛋白是广泛存在的核酸引导酶，通过互补碱基配对识别靶标。尽管在真核生物中，Agos 参与 RNA 沉默，但原核 Agos (pAgos) 的功能在很大程度上仍不清楚。特别是，一类截短和无催化活性的 pAgos（短 pAgos）缺乏表征。在这里，我们揭示了古菌 Sulfolobus islandicus 中的一种短 pAgo 蛋白与其两个遗传相关的蛋白 Aga1 和 Aga2 一起通过无效感染提供强大的抗病毒保护。Aga2 是一种毒性跨膜效应物，通过碱性口袋与阴离子磷脂结合，导致膜去极化和细胞杀伤。Ago 和 Aga1 形成一个稳定的复合物，表现出核酸指导的核酸识别能力，并直接与 Aga2 相互作用，指向一种免疫感应机制。总之，我们的研究结果强调了 pAgos 与其广泛相关蛋白之间的合作，表明存在未知多样性的 pAgo 衍生免疫系统。
