6vm6

Structural highlights

Function

CAP4_ACIS2 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(AAAA) CBASS system (PubMed:32839535).^{[1] [2]} Binds cyclic nucleotide second messengers (synthesized by CdnD, the cognate CD-NTase in the CBASS operon). Ligand binding activates it to endonucleolytically degrade dsDNA to approximately 6 bp length fragments, with a preference for 5'-C or 5'-G cleavage site. The minor product of CdnD is the activating nucleotide; also binds the major product (2',3',3'-cyclic AMP-AMP-AMP) but is not activated by it. Only binds DNA in the presence of ligand. Is not activated by c-di-AMP, c-di-GMP, 3'3'-cyclic GMP-AMP (3'3'-cGAMP) or 3',3',3'-cyclic AMP-AMP-GMP.^[3]

References

1. ↑ 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
2. ↑ Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ. CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection. Cell. 2020 Jun 4. pii: S0092-8674(20)30614-0. doi: 10.1016/j.cell.2020.05.019. PMID:32544385 doi:http://dx.doi.org/10.1016/j.cell.2020.05.019
3. ↑ Lowey B, Whiteley AT, Keszei AFA, Morehouse BR, Mathews IT, Antine SP, Cabrera VJ, Kashin D, Niemann P, Jain M, Schwede F, Mekalanos JJ, Shao S, Lee ASY, Kranzusch PJ. CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection. Cell. 2020 Jun 4. pii: S0092-8674(20)30614-0. doi: 10.1016/j.cell.2020.05.019. PMID:32544385 doi:http://dx.doi.org/10.1016/j.cell.2020.05.019