Structural highlights
Function
DNCV1_ECOLX CBASS (cyclic oligonucleotide-based antiphage signaling system) provides immunity against bacteriophage. The CD-NTase protein synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals. The signals activate a diverse range of effectors, leading to bacterial cell death and thus abortive phage infection. A type II-C(GA) CBASS system (PubMed:32839535).[1] Catalyzes the synthesis of 3'3'-cyclic GMP-AMP (3'3'-cGAMP) from GTP and ATP, a second messenger in cell signal transduction. Is also able to produce c-di-AMP and c-di-GMP from ATP and GTP, respectively; however, 3'3'-cGAMP is the dominant molecule produced by DncV in vivo, contrary to the 2'3'-cGAMP produced by eukaryotes. By producing cGAMP, down-regulates csgD expression and expression of flagellum regulon genes, which leads to the down-regulation of rdar biofilm formation and flagellum-mediated swimming and swarming motility in a temperature-dependent manner (PubMed:30837338). Controls the activity of cGAMP-activated phospholipase CapV, a patatin-like lipase that is a direct 3',3'-cGAMP receptor encoded in the dncV operon (By similarity).[UniProtKB:Q9KVG7][2]
Publication Abstract from PubMed
Cyclic dinucleotides (CDNs) play key roles as second messengers and signaling molecules in bacteria and metazoans. The newly identified dinucleotide cyclase in Vibrio cholerae (DncV) produces three different CDNs containing two 3'-5' phosphodiester bonds, and its predominant product is cyclic GMP-AMP, whereas mammalian cyclic GMP-AMP synthase (cGAS) produces only cyclic GMP-AMP containing mixed 2'-5' phosphodiester bonds. We report the crystal structures of V. cholerae and Escherichia coli DncV in complex with various nucleotides in the pre-reaction states. The high-resolution structures revealed that DncV preferably recognizes ATP and GTP as acceptor and donor nucleotides, respectively, in the first nucleotidyl transfer reaction. Considering the recently reported intermediate structures, our pre-reaction state structures provide the precise mechanism of 3'-5' linked cyclic AMP-GMP production in bacteria. A comparison with cGAS in the pre-reaction states suggests that the orientation of the acceptor nucleotide primarily determines the distinct linkage specificities between DncV and cGAS.
Structural Basis for the Catalytic Mechanism of DncV, Bacterial Homolog of Cyclic GMP-AMP Synthase.,Kato K, Ishii R, Hirano S, Ishitani R, Nureki O Structure. 2015 Apr 1. pii: S0969-2126(15)00078-7. doi:, 10.1016/j.str.2015.01.023. PMID:25865248[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Millman A, Melamed S, Amitai G, Sorek R. Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. Nat Microbiol. 2020 Dec;5(12):1608-1615. doi: 10.1038/s41564-020-0777-y. Epub, 2020 Aug 24. PMID:32839535 doi:http://dx.doi.org/10.1038/s41564-020-0777-y
- ↑ Li F, Cimdins A, Rohde M, Jänsch L, Kaever V, Nimtz M, Römling U. DncV Synthesizes Cyclic GMP-AMP and Regulates Biofilm Formation and Motility in Escherichia coli ECOR31. mBio. 2019 Mar 5;10(2):e02492-18. PMID:30837338 doi:10.1128/mBio.02492-18
- ↑ Kato K, Ishii R, Hirano S, Ishitani R, Nureki O. Structural Basis for the Catalytic Mechanism of DncV, Bacterial Homolog of Cyclic GMP-AMP Synthase. Structure. 2015 Apr 1. pii: S0969-2126(15)00078-7. doi:, 10.1016/j.str.2015.01.023. PMID:25865248 doi:http://dx.doi.org/10.1016/j.str.2015.01.023
