A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems

Zhang, Dapeng; Iyer, Lakshminarayan M.; Aravind, L.

Both actinomycetes and firmicutes do not display proteins with a PT domain with the VENN motif (PT-VENN). However, we observed that in both these lineages there was a conserved a-helical domain that frequently occurred just to the N-terminus of several distinct nuclease modules in different predicted toxins. This domain had a conserved TG motif and we accordingly named it the PT-TG domain ( Figure 5 Another domain, which we found frequently associated with several unrelated or distantly related nuclease domains from Gram-positive bacteria, was the Nuclease_N domain ( Figure 5, Supplementary Data) . It is predicted to be an a-helical domain and might also play a role in the delivery of the toxin module into the host cells. Toxins in the SUKH superfamily neighborhoods, irrespective of the type of the nuclease domain, can also be distinguished into two major architectural groups: one comprised of relatively small proteins with no notable stretches of repetitive sequence separating the N-from the C-terminal regions, and the second in which such repetitive sequences, such as the RHS and the filamentous hemagglutinin are present ( Figure 5 ). This might reflect a mechanistic difference in their mode of action: the smaller proteins could be soluble toxins that diffuse away from the cell producing it. In contrast, the large proteins with repetitive elements might form filamentous appendages that stick out from the cell-surface and depend primarily on contact with target cells for delivery [Hence, the latter group includes the recently characterized CDIs (25) ]. Alternatively, this difference might reflect the differences in the cell-wall structures of the bacterial lineages, with the smaller toxin proteins being more prevalent in the firmicutes. A subset of the smaller proteins with nuclease domains lack noticeable trafficking-related (N-terminal) domains. The corresponding genes could represent cassettes for alternative toxin modules that are linked by recombination to the larger full-length genes ( Figure 5 , see below).