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*

*Corresponding author for this work
29 Citations (Scopus)


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.

Original languageEnglish
JournalCell Host and Microbe
Issue number7
Pages (from-to)930-943.e6
Publication statusPublished - 13 Jul 2022


  • abortive infection
  • archaea
  • membrane depolarization
  • membrane-associated toxic effector
  • microbial antiviral defense system
  • nucleic-acid recognition
  • phospholipids-interacting protein
  • prokaryotic Argonaute


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