Key result
Csx28 forms an octameric pore-like structure that localizes to the inner membrane and enhances Cas13b-dependent antiviral defense by slowing cellular metabolism upon viral infection.
Csx28 acts as a downstream, Cas13b-dependent effector protein that uses membrane perturbation as an antiviral defense strategy in bacteria.
May guide engineering of prokaryotic defenses; leaves open analogous membrane effectors in eukaryotic antiviral pathways.
Type VI CRISPR-Cas systems use RNA-guided ribonuclease (RNase) Cas13 to defend bacteria against viruses, and some of these systems encode putative membrane proteins that have unclear roles in Cas13-mediated defense. We show that Csx28, of type VI-B2 systems, is a transmembrane protein that assists to slow cellular metabolism upon viral infection, increasing antiviral defense. High-resolution cryo-electron microscopy reveals that Csx28 forms an octameric pore-like structure. These Csx28 pores localize to the inner membrane in vivo. Csx28's antiviral activity in vivo requires sequence-specific cleavage of viral messenger RNAs by Cas13b, which subsequently results in membrane depolarization, slowed metabolism, and inhibition of sustained viral infection. Our work suggests a mechanism by which Csx28 acts as a downstream, Cas13b-dependent effector protein that uses membrane perturbation as an antiviral defense strategy.
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VanderWal et al. (2023) studied Viral infection in bacteria. Csx28 was evaluated on Antiviral defense and membrane depolarization. Csx28 forms an octameric pore-like structure that localizes to the inner membrane and enhances Cas13b-dependent antiviral defense by slowing cellular metabolism upon viral infection.
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