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TitlePhage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway.
Journal, issue, pagesNat Microbiol, Year 2024
Publish dateApr 22, 2024
AuthorsYan Yan / Jun Xiao / Fengtao Huang / Wei Xian / Bingbing Yu / Rui Cheng / Hui Wu / Xueling Lu / Xionglue Wang / Wenjing Huang / Jing Li / Greater Kayode Oyejobi / Carol V Robinson / Hao Wu / Di Wu / Xiaoyun Liu / Longfei Wang / Bin Zhu /
PubMed AbstractThe 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 ...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.
External linksNat Microbiol / PubMed:38649411
MethodsEM (single particle)
Resolution3.0 - 3.3 Å
Structure data

34992

8hsb

EMDB-34992, PDB-8hsb:
Cryo-EM Structure of CdnG-E2 complex from Serratia marcescens (UltrAuFoil)
Method: EM (single particle) / Resolution: 3.0 Å

39353

8yjy

EMDB-39353, PDB-8yjy:
Cryo-EM Structure of CdnG-E2 complex from Serratia marcescens
Method: EM (single particle) / Resolution: 3.3 Å

Source
  • serratia marcescens (bacteria)
KeywordsANTIVIRAL PROTEIN / cGAS / CdnG / E2 / CBASS

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