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PreprintCited by 125Bacteriophages and microbial interactionsCRISPR and Genetic EngineeringBacterial Genetics and Biotechnology

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Structural basis of Gabija anti-phage defense and viral immune evasion

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Antine, Sadie P., Johnson, Alex G., Mooney, Sarah E., Leavitt, Azita, Mayer, Megan L., Yirmiya, Erez, Amitai, Gil, Sorek, Rotem, Kranzusch, Philip J.·2023·Nature
DOI 10.1101/2023.05.01.538945PMC PMC10781630

Preprint — published as 10.1038/s41586-023-06855-2 · Paper page

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Abstract

Bacteria encode hundreds of diverse defense systems that protect from viral infection and inhibit phage propagation 1–5 . Gabija is one of the most prevalent anti-phage defense systems, occurring in >15% of all sequenced bacterial and archaeal genomes 1,6,7 , but the molecular basis of how Gabija defends cells from viral infection remains poorly understood. Here we use X-ray crystallography and cryo-EM to define how Gabija proteins assemble into an ∼500 kDa supramolecular complex that degrades phage DNA. Gabija protein A (GajA) is a DNA endonuclease that tetramerizes to form the core of the anti-phage defense complex. Two sets of Gabija protein B (GajB) dimers dock at opposite sides of the complex and create a 4:4 GajAB assembly that is essential for phage resistance in vivo . We show that a phage-encoded protein Gabija anti-defense 1 (Gad1) directly binds the Gabija GajAB complex and inactivates defense. A cryo-EM structure of the virally inhibited state reveals that Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage. Our results reveal the structural basis of assembly of the Gabija anti-phage defense complex and define a unique mechanism of viral immune evasion.

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Metadata

Authors
Antine, S. P., Johnson, A. G., Mooney, S. E., Leavitt, A., Mayer, M. L., Yirmiya, E., Amitai, G., Sorek, R., & Kranzusch, P. J.
Affiliations
  • Harvard University (US)
  • Weizmann Institute of Science (IL)
Corresponding author
Kranzusch, Philip J.
ORCID
Venue
Nature
Publisher
openRxiv
Published
2023-05-01
Volume
625
Issue
7994
Pages
360-365
ISSN
0028-0836 (ISSN-L)
DOI
10.1101/2023.05.01.538945
PMC
PMC10781630
OpenAlex
W4388913741
Cited by
125
References
1
Citations by year
2026: 40 · 2025: 42 · 2024: 33 · 2023: 9
FWCI
20.02
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • U.S. Department of Energy (DE‐ AC02‐06CH11357, AC02‐06CH11357, grid.436923.9, S10OD021527, P30 GM124165, S10RR029205, 06CH11357, 436923.9, DE-AC02-)
  • Burroughs Wellcome Fund (P30 GM124165)
  • Cancer Research Institute
  • Oregon Health and Science University (grid.436923.9, 436923.9)
  • Life Sciences Research Foundation
  • G. Harold and Leila Y. Mathers Foundation (P30 GM124165)
  • Parker Institute for Cancer Immunotherapy (P30 GM124165)
  • Mark Foundation For Cancer Research (P30 GM124165)
  • Open Philanthropy Project
  • Deutsche Forschungsgemeinschaft (464312965, DE-AC02-06CH11357, SPP2330)
  • Israel Science Foundation (MAPATS Grant 2720/22)
  • Council for Higher Education
  • National Institutes of Health (1dp2gm146250-01, 1s10od021527-01, DE-AC02–06CH11357, GM124165)
  • Office of Science (AC02‐06CH11357, DE-AC02, 06CH11357, grid.436923.9, DE-AC02-06CH11357)
  • National Institute of General Medical Sciences (DP2 GM146250, U24GM129547, P30GM124165)
  • National Center for Research Resources (S10RR029205)
  • Division of Chemistry
  • Biological and Environmental Research (DEAC0206CH11357, S10OD021527, P30 GM124165, grid.436923.9)
  • Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, 06CH11357, P30 GM124165)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
phage resistance, viral immune evasion, protein complex formation, protein tetramerization, phage-host interactions
MeSH terms
Bacteria, Bacterial Proteins, Bacteriophages, Deoxyribonucleases, DNA, Viral, Crystallography, X-Ray, Cryoelectron Microscopy, Protein Multimerization, Immune Evasion

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