Novel two-component system-like elements reveal functional domains associated with restriction-modification systems and paraMORC ATPases in bacteria

Abstract

BackgroundTwo-component systems (TCS) are essential machineries allowing for efficient signal recognition and transmission in bacterial cells. The majority of TCSs utilized by bacteria are composed by a sensor histidine kinase (HK) and a cognate response regulator (RR). In the present study, we report two newly predicted protein domains -- Response_reg_2 (PF19192) and HEF_HK (PF19191) -- in bacteria which exhibit high structural similarity, respectively, with typical domains of RRs and HKs. ResultsAdditionally, the genes encoding for the novel predicted domains exhibit a 91.6% linkage observed across 644 genomic regions recovered from 628 different bacterial strains. The remarkable adjacent co-localization between genes carrying Response_reg_2 and HEF_HK in addition to their conserved structural features, which are highly similar to those from well-known HKs and RRs, raises the possibility of Response_reg_2 and HEF_HK integrating a new TCS in bacteria. The genomic regions in which these predicted two-component systems-like are located additionally exhibit an overrepresented presence of restriction-modification (R-M) systems especially the type II R-M. Among these, there is a conspicuous presence of C-5 cytosine-specific DNA methylases which may indicate a functional association with the newly discovered domains. The solid presence of R-M systems and the presence of the GHKL family domain HATPase_c_3 across most of the HEF_HK-containing genes are also indicative that these genes are evolutionarily related to the paraMORC family of ATPases. ConclusionsThe present study uncovered two novel protein conserved domains and raised the possibility of a TCS-like system undertaking a regulatory role mechanistically linked to R-M systems in a large variety of bacterial lineages.