8HSB

Cryo-EM Structure of CdnG-E2 complex from Serratia marcescens (UltrAuFoil)

Summary for 8HSB

• Entry DOI: 10.2210/pdb8hsb/pdb
• EMDB information: 34992
• Descriptor: CdnG, Type VI secretion protein (2 entities in total)
• Functional Keywords: cgas, cdng, e2, cbass, antiviral protein
• Biological source: Serratia marcescens; More
• Total number of polymer chains: 2
• Total formula weight: 64264.38

Authors

Xiao, J.,Wang, L. (deposition date: 2022-12-18, release date: 2024-05-01, Last modification date: 2025-06-25)

Primary citation

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.
Phage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway.
Nat Microbiol, 9:1566-1578, 2024

PubMed 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.

PubMed: 38649411
DOI: 10.1038/s41564-024-01684-z

Experimental method

ELECTRON MICROSCOPY (3 Å)