PrrC tRNA anticodon nuclease and T4 exclusion system. A) The E. coli hsd gene cluster includes prrC. B) PrrC has N-terminal two thirds NTPase and Eco prrI interaction domains and, starting at residue 265, C-terminal tRNA recognition and ribonuclease (ACNase) catalytic domains. C) Current model for tRNA cleavage and T4 exclusion. i) PrrC, minimally as a head-to-tail dimer (tetramer and hexamer oligomers are possible) associates with Eco prrI on DNA, as an inactive, latent endoribonuclease. ii) In one of two allosteric activation mechanisms, Eco prrI-PrrC-DNA complex binds increased levels of dTTP and with GTP hydrolysis activated ACNase cleaves the anticodon of tRNALys. iii) During infection, the small, T4-encoded polypeptide stp binds Eco prrI activating tRNALys ACNase. iv) T4 repairs the cleaved tRNA at the 2',3'cyclic phosphate and 5' OH using polynucleotide kinase (Pnk) and RNA ligase (Rnl1). Figure adapted from the publications of Kaufmann and colleagues [111, 114, 116, 119].