Search

The Gabija complex is a prokaryotic antiviral system consisting of the GajA and GajB proteins. GajA was identified as a DNA nicking endonuclease but the functions of GajB and the complex remain unknown. Here, we show that synergy between GajA-mediated DNA cleavage and nucleotide hydrolysis by GajB initiates efficient abortive infection defense against virulent bacteriophages. The antiviral activity of GajA requires GajB, which senses DNA termini produced by GajA to hydrolyze (d)A/(d)GTP, depleting essential nucleotides. This ATPase activity of Gabija complex is only activated upon DNA binding. GajA binds to GajB to form stable complexes in vivo and in vitro. However, a functional Gabija complex requires a molecular ratio between GajB and GajA below 1:1, indicating stoichiometric regulation of the DNA/nucleotide processing complex. Thus, the Gabija system exhibits distinct and efficient antiviral defense through sequential sensing and activation of nucleotide depletion and DNA cleavage, causing a cascade suicide effect. [Display omitted] • GajB senses DNA termini to hydrolyze (d)A/(d)GTP • The functional Gabija complex necessitates a higher molecular ratio of GajA to GajB • The synergy between GajA and GajB results in an efficient abortive infection • Both GajA and GajB exhibit a dual role by functioning as signal sensors and effectors Cheng et al. reveal the molecular mechanism of the widespread Gabija prokaryotic immune system, in which the synergy between GajA, an NTP-sensing DNA nickase, and GajB, a DNA-terminus-dependent (d)A/(d)GTPase, causes a cascade suicide effect to mediate defense against virulent viruses. [ABSTRACT FROM AUTHOR]