A short prokaryotic Argonaute activates membrane effector to confer antiviral defense

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

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
Volume30
Issue number7
Pages (from-to)930-943.e6
Number of pages21
ISSN1931-3128
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc.

    Research areas

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

ID: 321260031