Structural highlights
Publication Abstract from PubMedThe bacterial anti-phage immune system is complex, diverse, and in several important cases ancestral to that found in eukaryotes, including humans. One example is CBASS (cyclic oligonucleotide based anti-phage signalling system), a widespread bacterial defence that signals phage presence in the cell via cyclic nucleotide second messengers, activating ancillary effectors to combat infection. CBASS is homologous and ancestral to the eukaryotic cGAS/STING pathway for antiviral defence. The heart of the system is a nucleotide cyclase known as a cGAS/DncV-like nucleotidyltransferase, which is activated by phage infection. The mechanisms of activation of CBASS cyclases are diverse and in most cases not fully understood at a molecular level. Moreover, it is vital to keep these signal-generating enzymes fully inactive in the absence of phage infection to avoid auto-toxicity. Here, we report a structural and mechanistic study of a CBASS cyclase from Bacillus cereus. Using crystal structures of key reaction intermediates, coupled with kinetic analyses, we show that the substrate, ATP, plays a fundamental role in the inhibition of the non-activated form of the enzyme in vitro. We provide a molecular explanation for this regulation and explore the implications for the regulation of these important defence systems in bacterial immunity. Inhibition by ATP regulates the activity of a CBASS anti-phage nucleotide cyclase.,Gaskell-Mew L, McQuarrie S, McMahon SA, Wotherspoon P, Graham S, Gloster TM, White MF Biochem J. 2026 Aug 5;483(8):1617-1630. doi: 10.1042/BCJ20260457. PMID:42496152[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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