统一核酸酶-蛋白酶机制介导抗病毒防御

In this work, we present evidence for a unified nuclease- protease mechanism common to multiple antiviral systems with different infection- sensing mechanisms in bacteria. Cell- based and biochemical assays show that the nuclease exists initially as an enzymatically inac- tive “gated” proenzyme. Site- specific cleavage by the partner protease liberates the nuclease active site. We show that the activated nuclease is specific for DNA and executes indiscriminate DNA cleavage to re- strict viral replication. This mechanism is similar in otherwise unre- lated immune systems, suggesting that coordination between the nuclease and protease is conserved in immune systems with different modes of infection sensing. Phylogenetic analysis revealed that gated nuclease homologs additionally exist in genomic loci alongside caspase- family proteases. …