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

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Filamentation activates bacterial Avs5 antiviral protein

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Wang, Yiqun, Tian, Yuqing, Yang, Xu, Yu, Feng, Zheng, Jianting·2025·Nature Communications
DOI 10.1038/s41467-025-57732-7PMC PMC11897194

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Abstract

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. EfAvs5, 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 EfAvs5 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 EfAvs5. EfAvs5 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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Metadata

Authors
Wang, Y., Tian, Y., Yang, X., Yu, F., & Zheng, J.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
Zheng, Jianting
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-03-11
Volume
16
Issue
1
Pages
2408-2408
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-025-57732-7
PMC
PMC11897194
OpenAlex
W4408312757
Cited by
18
References
4
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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