This was a very fruitful collaboration with @ostermanilya.bsky.social 🙌 Thanks to all co-authors, and reviewers who provided us with very constructive comments.

The C-terminal domains of the caspase-like protease dimer form a putative pocket that is predicted by AF3 to bind N7-cADPR. During the revisions, @ostermanilya.bsky.social showed that mutations in this pocket abolish defense, supporting that this pocket indeed serves to bind N7-cADPR.

Once produced, this molecule activates the caspase-like protein into a promiscuous arginine-specific protease that cleaves dozens of cellular proteins to halt infection, a process reminiscent of human executioner caspases.

In short, we show that during phage infection, the TIR-domain protein uses NAD+ to produce a novel signaling molecular that we called N7-cADPR.

WOW 🤩 Outstanding talk by @pilhoferlab.bsky.social at @ciri-lyon.bsky.social on bacterial nano-weapons mediating microbial warfare 🗡🛡