A short prokaryotic Argonaute activates membrane effector to confer antiviral defense
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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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cell Host and Microbe |
| Vol/bind | 30 |
| Udgave nummer | 7 |
| Sider (fra-til) | 930-943.e6 |
| Antal sider | 21 |
| ISSN | 1931-3128 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The research was supported by National Key Research and Development program of China (2019YFA0906400), National Science Foundation of China (grant no. 31970545), Fundamental Research Funds for Central Universities (grant no. 2662020SKPY001), the Foundation of Hubei Hongshan Laboratory (no. 2021hszd022), and Huazhong Agricultural University Scientific & Technological Self-Innovation Foundation. R.P-R. was financed by the Lundbeck Foundation (Lundbeckfonden), postdoc grant R347-2020-2346. S.A.S. is a recipient of a Novo Nordisk Foundation project grant in basic bioscience (NNF18OC0052965). C.Z. and R.J.W. were supported by U.S National Science Foundation under IOS grant award no. 1656869. We thank the core facilities of Center for Protein Research (CPR), the State Key Laboratory of Agricultural Microbiology Core Facility and the Experimental Teaching Center of Bioengineering at Huazhong Agricultural University for technical support. Z.Z. Y.C. Z.H. and C. Wu conducted the experiments. S.A.S. and R.P-R. performed bioinformatics analysis. F.Z. and C. Wang predicted and analyzed the structures. C.Z. R.J.W. and Q.S. provided archaeal materials. R.P-R. C.Z. R.J.W. and Q.S. critically commented the draft. W.H. acquired the funding, supervised the work, and wrote the original draft. All authors contributed to review and editing. The authors declare no competing interests.
Funding Information:
The research was supported by National Key Research and Development program of China ( 2019YFA0906400 ), National Science Foundation of China (grant no. 31970545 ), Fundamental Research Funds for Central Universities (grant no. 2662020SKPY001 ), the Foundation of Hubei Hongshan Laboratory (no. 2021hszd022 ), and Huazhong Agricultural University Scientific & Technological Self-Innovation Foundation . R.P-R. was financed by the Lundbeck Foundation (Lundbeckfonden), postdoc grant R347-2020-2346 . S.A.S. is a recipient of a Novo Nordisk Foundation project grant in basic bioscience ( NNF18OC0052965 ). C.Z. and R.J.W. were supported by U.S National Science Foundation under IOS grant award no. 1656869 . We thank the core facilities of Center for Protein Research (CPR), the State Key Laboratory of Agricultural Microbiology Core Facility and the Experimental Teaching Center of Bioengineering at Huazhong Agricultural University for technical support.
Publisher Copyright:
© 2022 Elsevier Inc.
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