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PreprintCited by 18Bacteriophages and microbial interactionsInvertebrate Immune Response MechanismsBacterial Genetics and Biotechnology

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Filamentation activates bacterial NLR-like antiviral protein

Open access
Zheng, Jianting, Wang, Yiqun, Tian, Yuqing, Yang, Xu, Yu, Feng·2024·Nature Communications
DOI 10.21203/rs.3.rs-5156926/v1PMC PMC11897194

Preprint — published as 10.1038/s41467-025-57732-7 · Paper page

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Abstract

Bacterial antiviral STANDs (Avs) are evolutionarily related to the nucleotide-binding leucine-rich repeat containing receptors (NLRs) widely distributed in immune systems across animals and plants. Ef Avs5, an Avs type 5 protein from Escherichia fergusonii, contains an N-terminal SIR2 effector domain, a nucleotide-binding oligomerization domain (NOD) and a C-terminal sensor domain, conferring protection against diverse phage invasions. Despite the established roles of SIR2 and STAND in prokaryotic and eukaryotic immunity, the mechanism underlying their collaboration remains unclear. Here we present cryo-EM structures of Ef Avs5 filaments, elucidating the mechanisms of dimerization, filamentation, filament clustering, ATP binding and NAD+ hydrolysis, all of which are crucial for anti-phage defense. The SIR2 domains and NODs engage in the intra- and inter-dimer interaction to form an individual filament, while the outward C-terminal domains contribute to bundle formation. Filamentation potentially stabilizes the dimeric SIR2 configuration, thereby activating the NADase activity of Ef Avs5. Ef Avs5 is deficient in the ATPase activity, but elevated ATP concentrations can impede its NADase activity. Together, we uncover the filament assembly of Avs5 as a unique mechanism to switch enzyme activities and perform anti-phage defenses, emphasizing the conserved role of filamentation in immune signaling across diverse life forms.

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Research works printed but not linked: 41

  1. Millman A et al (2022) An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30:1556–1569e1555. https://doi.org:10.1016/j.chom.2022.09.017 · DOI · Paper page
  2. Vassallo CN, Doering CR, Littlehale ML, Teodoro GIC, Laub MT (2022) A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 7:1568–1579. https://doi.org:10.1038/s41564-022-01219-4 · DOI
  3. Gao L et al (2020) Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369:1077–1084. https://doi.org:10.1126/science.aba0372 · DOI
  4. Gao LA et al (2022) Prokaryotic innate immunity through pattern recognition of conserved viral proteins. Science 377. https://doi.org:10.1126/science.abm4096 · DOI
  5. Huang S et al (2023) NLR signaling in plants: from resistosomes to second messengers. Trends Biochem Sci 48:776–787. https://doi.org:10.1016/j.tibs.2023.06.002 · DOI
  6. Mitchell PS, Sandstrom A, Vance RE (2019) The NLRP1 inflammasome: new mechanistic insights and unresolved mysteries. Curr Opin Immunol 60:37–45. https://doi.org:10.1016/j.coi.2019.04.015 · DOI
  7. Koopal B et al (2022) Short prokaryotic Argonaute systems trigger cell death upon detection of invading DNA. Cell 185:1471–1486e1419. https://doi.org:10.1016/j.cell.2022.03.012 · DOI
  8. Ka D, Oh H, Park E, Kim J-H, Bae E (2020) Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD + degradation. Nat Commun 11. https://doi.org:10.1038/s41467-020-16703-w · DOI
  9. Garb J et al (2022) Multiple phage resistance systems inhibit infection via SIR2-dependent NAD + depletion. Nat Microbiol 7:1849–1856. https://doi.org:10.1038/s41564-022-01207-8 · DOI
  10. Tang D et al (2023) Multiple enzymatic activities of a Sir2-HerA system cooperate for anti-phage defense. Mol Cell 83:4600–4613e4606. https://doi.org:10.1016/j.molcel.2023.11.010 · DOI
  11. Tamulaitiene G et al (2024) Activation of Thoeris antiviral system via SIR2 effector filament assembly. Nature. https://doi.org:10.1038/s41586-024-07092-x · DOI
  12. Yang X, Wang Y, Zheng J (2024) Structural insights into autoinhibition and activation of defense-associated sirtuin protein. Int J Biol Macromol 277:134145. https://doi.org:10.1016/j.ijbiomac.2024.134145 · DOI
  13. Fillol-Salom A et al (2022) Bacteriophages benefit from mobilizing pathogenicity islands encoding immune systems against competitors. Cell 185:3248–3262e3220. https://doi.org:10.1016/j.cell.2022.07.014 · DOI
  14. Morehouse BR et al (2022) Cryo-EM structure of an active bacterial TIR–STING filament complex. Nature 608:803–807. https://doi.org:10.1038/s41586-022-04999-1 · DOI
  15. Hogrel G et al (2022) Cyclic nucleotide-induced helical structure activates a TIR immune effector. Nature 608:808–812. https://doi.org:10.1038/s41586-022-05070-9 · DOI · Paper page
  16. Du J et al (2011) Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334:806–809. https://doi.org:10.1126/science.1207861 · DOI · Paper page
  17. Yin H et al (2024) Insights into the modulation of bacterial NADase activity by phage proteins. Nat Commun 15. https://doi.org:10.1038/s41467-024-47030-z · DOI
  18. Kaur G, Iyer LM, Burroughs AM, Aravind L (2021) Bacterial death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans. Elife 10. https://doi.org:10.7554/eLife.70394 · DOI
  19. Holm L (2022) Dali server: structural unification of protein families. Nucleic Acids Res 50:W210–w215. https://doi.org:10.1093/nar/gkac387 · DOI
  20. Wang J et al (2019) Reconstitution and structure of a plant NLR resistosome conferring immunity. Science 364. https://doi.org:10.1126/science.aav5870 · DOI
  21. Zhou M et al (2015) Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. Genes Dev 29:2349–2361. https://doi.org:10.1101/gad.272278.115 · DOI
  22. Xiao L, Magupalli VG, Wu H (2023) Cryo-EM structures of the active NLRP3 inflammasome disc. Nature 613:595–600. https://doi.org:10.1038/s41586-022-05570-8 · DOI
  23. Ma S et al (2020) Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme. Science 370. https://doi.org:10.1126/science.abe3069 · DOI
  24. Wang J et al (2019) Reconstitution and structure of a plant NLR resistosome conferring immunity. Science 364. https://doi.org:10.1126/science.aav5870 · DOI
  25. Pang Y et al (2015) Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila. Genes Dev 29:277–287. https://doi.org:10.1101/gad.255877.114 · DOI
  26. Ma S et al (2024) Oligomerization-mediated autoinhibition and cofactor binding of a plant NLR. Nature 632:869–876. https://doi.org:10.1038/s41586-024-07668-7 · DOI
  27. Zhang Y, Dorey S, Swiderski M, Jones JD (2004) Expression of RPS4 in tobacco induces an AvrRps4-independent HR that requires EDS1, SGT1 and HSP90. Plant J 40:213–224. https://doi.org:10.1111/j.1365-313X.2004.02201.x · DOI
  28. Horsefield S et al (2019) NAD(+) cleavage activity by animal and plant TIR domains in cell death pathways. Science 365:793–799. https://doi.org:10.1126/science.aax1911 · DOI
  29. Conte AN et al (2024) https://doi.org:10.1101/2024.06.04.597415 · DOI
  30. Song W et al (2024) Substrate-induced condensation activates plant TIR domain proteins. Nature 627:847–853. https://doi.org:10.1038/s41586-024-07183-9 · DOI
  31. Punjani A, Rubinstein JL, Fleet DJ, Brubaker MA (2017) cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat Methods 14:290–296. https://doi.org:10.1038/nmeth.4169 · DOI · Paper page
  32. Casanal A, Lohkamp B, Emsley P (2020) Current developments in Coot for macromolecular model building of Electron Cryo-microscopy and Crystallographic Data. Protein Sci 29:1069–1078. https://doi.org:10.1002/pro.3791 · DOI
  33. Pettersen EF et al (2021) UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci 30:70–82. https://doi.org:10.1002/pro.3943 · DOI
  34. Liebschner D et al (2019) Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr D Struct Biol 75:861–877. https://doi.org:10.1107/S2059798319011471 · DOI · Paper page
  35. Tesson F et al (2022) Systematic and quantitative view of the antiviral arsenal of prokaryotes. Nat Commun 13:2561. https://doi.org:10.1038/s41467-022-30269-9 · DOI
  36. van Kempen M et al (2024) Fast and accurate protein structure search with Foldseek. Nat Biotechnol 42:243–246. https://doi.org:10.1038/s41587-023-01773-0 · DOI · Paper page
  37. Steinegger M, Söding J (2017) MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets. Nat Biotechnol 35:1026–1028. https://doi.org:10.1038/nbt.3988 · DOI · Paper page
  38. Katoh K, Rozewicki J, Yamada K (2019) D. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinform 20:1160–1166. https://doi.org:10.1093/bib/bbx108 · DOI · Paper page
  39. Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T (2009) trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25:1972–1973. https://doi.org:10.1093/bioinformatics/btp348 · DOI
  40. Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ (2015) IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 32:268–274. https://doi.org:10.1093/molbev/msu300 · DOI · Paper page
  41. Letunic I, Bork P (2021) Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 49:W293–w296. https://doi.org:10.1093/nar/gkab301 · DOI

Metadata

Authors
Zheng, J., Wang, Y., Tian, Y., Yang, X., & Yu, F.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
Zheng, Jianting
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-10-15
Volume
16
Issue
1
Pages
2408-2408
ISSN
2041-1723 (ISSN-L)
DOI
10.21203/rs.3.rs-5156926/v1
PMC
PMC11897194
OpenAlex
W4408312757
Cited by
18
References
1
Citations by year
2026: 12 · 2025: 6
FWCI
9.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (32370071, 32070040)
  • National Key Research and Development Program of China
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
filamentation, nucleotide-binding oligomerization domain, NOD-like receptors, Escherichia fergusonii, phage defense, NADase activity, filament bundling, ATP binding, protein dimerization, cryo-EM structure
MeSH terms
Protein Domains, Adenosine Triphosphate, Bacterial Proteins, Models, Molecular, NAD, Protein Binding, Bacteriophage T7, Cryoelectron Microscopy, Protein Multimerization

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