Feng et al. uncover how a bacterial immune effector, KomBC, is activated by the toxic nucleotide dITP. A preassembled filament converts sparse, non-cyclic dITP signals into cooperative NADase activation, revealing a distinct ultrasensitive immune mechanism.

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Signaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. Whereas cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of othe...

Recently, the Kongming system has been identified as a bacterial anti-phage defense system relied on nucleobase-modified nucleotides for immune signaling. Zhen et al. determine a series of cryo-EM structures of this system, revealing that dITP binding induces filament assembly of KomBC, which elucidats the activation mechanism of the Kongming system.

Several antiviral immune systems based on nucleotide signaling have been identified in bacteria. One of them is the Kongming system, which includes an effector complex (KomBC), composed of a non-canonical purine NTP pyrophosphatase (KomB) and a SIR2 domain-containing protein (KomC). The Kongming system is activated by an atypical signaling nucleotide, dITP, generated upon phage infection. Here, we use structural and functional analyses to show that KomBC assembles into a helical filament, built from vertically stacked 4:4 KomB–KomC repeating units. Binding of dITP to KomB initiates progressive conformational rearrangements within the filament, ultimately remodeling the filament into a distinct architecture in which KomC adopts an active conformation with NADase activity. We further identify a key residue potentially involved in the acquisition of NADase activity in SIR2 family proteins. Thus, our results elucidate the activation mechanism of KomBC, revealing a distinct mode of effector

Some bacteria use the so-called Kongming immune system, based on nucleotide signaling, to respond to viral infections. Here, the authors show that the Koming effector complex assembles into a helical filament, and the signaling nucleotide induces conformational rearrangements that activate an NADase activity leading to death of infected cells.