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Cited by 29Bacteriophages and microbial interactionsinterferon and immune responsesBacterial Genetics and Biotechnology

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Phage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway

Open access
Yan, Yan, Xiao, Jun, Huang, Fengtao, Xian, Wei, Yu, Bingbing, Cheng, Rui, Wu, Hui, Lu, Xueling, Wang, Xionglue, Huang, Wenjing, Li, Jing, Oyejobi, Greater Kayode, Robinson, Carol V., Wu, Hao, Wu, Di, Liu, Xiaoyun, Wang, Longfei, Zhu, Bin·2024·Nature Microbiology
DOI 10.1038/s41564-024-01684-z

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Abstract

The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homologue of eukaryotic ubiquitin-conjugating enzymes, which is either an E1-E2 fusion or a single E2. However, the functions of single E2s in CBASS remain elusive. Here, using biochemical, genetic, cryo-electron microscopy and mass spectrometry investigations, we discover that the E2 enzyme from Serratia marcescens regulates cGAS by imitating the ubiquitination cascade. This includes the processing of the cGAS C terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond and poly-cGASylation. The poly-cGASylation activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Thus, our findings reveal a unique regulatory role of E2 in CBASS.

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Metadata

Authors
Yan, Y., Xiao, J., Huang, F., Xian, W., Yu, B., Cheng, R., Wu, H., Lu, X., Wang, X., Huang, W., Li, J., Oyejobi, G. K., Robinson, C. V., Wu, H., Wu, D., Liu, X., Wang, L., & Zhu, B.
Affiliations
  • Huazhong University of Science and Technology (CN)
  • Wuhan University (CN)
  • Peking University (CN)
  • Boston Children's Hospital (US)
  • University of Oxford (GB)
Corresponding author
  • Huang, Fengtao
  • Wu, Di
  • Liu, Xiaoyun
  • Wang, Longfei
  • Zhu, Bin
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2024-04-22
Volume
9
Issue
6
Pages
1566-1578
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-024-01684-z
OpenAlex
W4395010496
Cited by
29
References
1
Citations by year
2026: 6 · 2025: 14 · 2024: 6
FWCI
7.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Microbiology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (32150009, 31870165, 31900032, 22174003, 21974002)
  • Science, Technology and Innovation Commission of Shenzhen Municipality
  • 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 › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
C-BASS, cGAS, E2 ubiquitin-conjugating enzyme, Serratia marcescens, cGAMP, antiviral innate immunity, phage defense, cell death
MeSH terms
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Bacterial Proteins, Bacteriophages, Humans, Immunity, Innate, Nucleotides, Cyclic, Nucleotidyltransferases, Signal Transduction, Cryoelectron Microscopy, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitination

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