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.

Although there has been gene loss in several eukaryotic lineages, at least the two ancient versions, namely PGs2 and FBXO3 appear to have been largely vertically inherited and show no lineage-specific expansions within eukaryotes. This is in sharp contrast to the high propensity for lateral transfer and for lineage-specific expansions of the SUKH superfamily that is observed in bacteria. This feature, together with the available functional evidence suggests that these conserved eukaryotic versions have acquired a biological role distinct from that in the toxin-immunity systems of bacteria. Nevertheless, there were several features that suggested to us that biochemically the eukaryotic versions might be exploiting an ancient functional template provided by the SUKH domains in bacterial nuclease toxin systems. Firstly, the studies on yeast Smi1/Knr4 have shown that it interacts with a large number of structurally and functionally distinct proteins (19) . In FBXO3, and independently in the above-mentioned fungal proteins, it appears in a domain architectural context corresponding to the part of the E3 F-box subunit that recognizes the substrate for ubiquitination (74) . This suggests that it might be deployed as a recognition domain to recruit particular substrates for ubiquitination. In bacteria the SUKH superfamily domains are one of the most widespread immunity proteins that appear to function in conjunction with a repertoire of nuclease toxins that are extremely diverse in sequence and structure (Figures 3 and 4) . Taken as a whole, these observations indicate that the SUKH domain contains a scaffold that has been adapted to recognize a diverse set of protein partners.