By analogy for the PrrC PrrI linkage, we propose that these associations amongst R M methods and HEPN domains signify distinct multi pronged defense strategies. A subset of RloC like ABC HEPN proteins are encoded inside of mobile gene neighborhoods that in addi tion to genes for R M elements, also encode a toxin in the DOC superfamily. The DOC domains perform by NMPylating serines and threonines in target proteins and therefore are contained inside a broad wide variety of harmful toxins like TA techniques, polymorphic toxins and secreted effectors of pathogens. These genomic associations suggest the respective defense systems physical exercise a 3 level defense method which targets invading DNA via the R M program, RNA by means of the HEPN protein, in all probability by inhibition of translation, and proteins through the DOC toxin.
Inside a related vein, we observed that some PrrC like pro teins are encoded by genomic loci that mix genes for R M system components TWS119 structure and those for RhuM like pro teins, which had been previously observed in pathogenicity islands of Salmonella. In these gene neighborhoods the RhuM like protein occupies a place similar to that of the DOC toxin within the neighborhoods mentioned above, and without a doubt the RhuM like domain these details is often fused for the DOC domain. Based mostly on this association, we propose that RhuM can also be a toxin domain that might function through professional tein modification as aspect of the multilevel defense system, jointly with all the PrrC like and RM proteins. We also located that various HEPN domains from the Ymh loved ones are fused for the C termini of ATPases of your GHKL superfamily, often known as paraMORCs, in proteins encoded by genes embedded in R M procedure gene neigh borhoods. The paraMORC domains, while unrelated to SbcC Rad50 ABC ATPases, appear to function analo gous towards the latter in both R M together with other contexts.
Consequently, we propose that these Ymh proteins represent an independent emergence of the domain architecture that is definitely functionally analogous to PrrC and RloC. Several families of HEPN domains show independent fusions to one particular or additional of four distinct households of endoDNase domains identified in R M methods, namely do mains of your REase fold, HNH EndoVII fold, ParB like fold and HKD phospholipase D fold. Furthermore, we recognized a number of, independent fusions with the HEPN domain with SWI2 SNF2 helicases, EcoEI like superfamily II helicases and SF I helicases, which are the helicase subunits observed in quite a few distinct R M techniques. In one such group of giant proteins, furthermore to a fusion to your HEPN domain, the SF I helicase can also be fused to a transglutaminase like peptidase, a REase fold DNase from the very brief patch fix relatives and winged helix turn helix domains. In another class of R M methods, a HEPN domain of your Abi2 SWT1 household is fused to a distinct version from the AAA ATPase domain.