A short prokaryotic Argonaute activates membrane effector to confer antiviral defense.

Zhifeng Zeng, Yu Chen, Rafael Pinilla-Redondo, Shiraz A Shah, Fen Zhao, Chen Wang, Zeyu Hu, Chang Wu, Changyi Zhang, Rachel J Whitaker, Qunxin She, Wenyuan Han

Cell host & microbe 2022 Jul 13

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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. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Zhifeng Zeng, Yu Chen, Rafael Pinilla-Redondo, Shiraz A Shah, Fen Zhao, Chen Wang, Zeyu Hu, Chang Wu, Changyi Zhang, Rachel J Whitaker, Qunxin She, Wenyuan Han. A short prokaryotic Argonaute activates membrane effector to confer antiviral defense. Cell host & microbe. 2022 Jul 13;30(7):930-943.e6