Structural Superimposition

Abstact

Abortive infection systems protect bacteria by triggering self-destruction in response to phage attack. Most known systems rely on stable cyclic nucleotides that accumulate to stoichiometric levels to activate effectors; the Kongming (Kom) system employs the toxic metabolite deoxyinosine triphosphate (dITP) as its signaling molecule. Here, we show that the Escherichia coli KomB-KomC (KomBC) complex forms a preassembled filament that remains inactive until dITP binding induces cooperative allosteric activation. KomB, a homolog of the nucleotide-hydrolyzing enzyme HAM1, has lost catalytic activity but evolved a high-affinity, hydrolysis-resistant binding pocket for dITP. Interestingly, substoichiometric dITP binding is sufficient to activate adjacent KomC NADase domains, which propagate activation cooperatively along the filament. This filament-based architecture enables ultrasensitive, long-range allosteric signaling in response to a low-abundance and short-lived metabolite. Our findings reveal an ultrasensitive immune strategy that transforms a toxic byproduct into a robust antiviral trigger, expanding the known repertoire of bacterial defense strategies.