Structures and activation mechanism of the Gabija anti-phage system
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Abstract
Prokaryotes have evolved intricate innate immune systems against phage infection 1-7. Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB 8. GajA functions as a DNA endonuclease that is inactive in the presence of ATP 9. Here, to explore how the Gabija system is activated for anti-phage defence, we report its cryo-electron microscopy structures in five states, including apo GajA, GajA in complex with DNA, GajA bound by ATP, apo GajA-GajB, and GajA-GajB in complex with ATP and Mg 2+. GajA is a rhombus-shaped tetramer with its ATPase domain clustered at the centre and the topoisomerase-primase (Toprim) domain located peripherally. ATP binding at the ATPase domain stabilizes the insertion region within the ATPase domain, keeping the Toprim domain in a closed state. Upon ATP depletion by phages, the Toprim domain opens to bind and cleave the DNA substrate. GajB, which docks on GajA, is activated by the cleaved DNA, ultimately leading to prokaryotic cell death. Our study presents a mechanistic landscape of Gabija activation.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
ColabFold - Making protein folding accessible to all
Mirdita, M., Schütze, K., Moriwaki, Y., Heo, L., Ovchinnikov, S., & Steinegger, M. (2021) · doi:10.1101/2021.08.15.456425 · Cited by 9,391 · see citing works
Structural basis of Gabija anti-phage defence and viral immune evasion
Antine, S. P., Johnson, A. G., Mooney, S. E., Leavitt, A., Mayer, M. L., Yirmiya, E., Amitai, G., Sorek, R., & Kranzusch, P. J. (2024) · Nature · doi:10.1038/s41586-023-06855-2 · Cited by 125 · see citing works
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- Authors
- Li, J., Cheng, R., Wang, Z., Yuan, W., Xiao, J., Zhao, X., Du, X., Xia, S., Wang, L., Zhu, B., & Wang, L.
- Affiliations
- Wuhan University (CN)
- Huazhong University of Science and Technology (CN)
- California Institute of Technology (US)
- Corresponding author
- Wang, Lianrong
- Zhu, Bin
- Wang, Longfei
- ORCID
- Venue
- Nature
- Published
- 2024-03-12
- Volume
- 629
- Issue
- 8011
- Pages
- 467-473
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4392697373
- Cited by
- 46
- References
- 3
- Citations by year
- 2026: 21 · 2025: 20 · 2024: 5
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- green
- dx.doi.org
- Licence
- Locations
- Nature (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- California Institute of Technology
- National Natural Science Foundation of China (32150009)
- Wuhan University
- Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20210324115811032)
- National Key Research and Development Program of China
- Topics
- Physical Sciences › Environmental Science › Ecology › 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 defense, DNA endonuclease, ATPase domain, protein structure, activation mechanism, ATP depletion, DNA cleavage, protein tetramer, cryo-electron microscopy
- MeSH terms
- Protein Domains, Adenosine Triphosphatases, Adenosine Triphosphate, Apoproteins, Bacillus cereus, Bacterial Proteins, Bacteriophages, DNA, Immunity, Innate, Magnesium, Models, Molecular, Protein Binding, DNA Primase, Cryoelectron Microscopy, Protein Structure, Quaternary, DNA Topoisomerases, Microbial Viability, DNA Cleavage
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