Thiol-based redox sensing in the methyltransferase associated sensor kinase RdmS in Methanosarcina acetivorans.

Abstract

Organisms have evolved signal transduction systems to quickly adapt their lifestyle to internal and environmental changes. While protein kinases and two-component systems are widely distributed in Bacteria, they are also found in Archaea but are less diversified and abundant. In this work, we analysed the function of the kinase RdmS and its role in a putative two-component system in the methanogenic archaeon Methanosarcina acetivorans. RdmS is encoded upstream of the regulator MsrF, which activates the expression of the corrinoid/methyltransferase fusion protein MtsD. In contrast to a typical bacterial histidine kinase, RdmS lacks a membrane domain and the conserved histidine residue for phosphorylation, indicating a different mechanism of signal transduction in comparison to bacterial counterparts. RdmS covalently binds a heme cofactor and is thereby able to bind small molecules like CO and dimethyl sulfide. Interestingly, RdmS possesses a redox-dependent autophosphorylation activity, which, however, is independent of the bound heme cofactor. In fact, our experimental data suggest a thiol-based redox sensing mechanism by RdmS. Moreover, we were able to show that RdmS interacts with the regulator protein MsrF. From these data, we conclude RdmS to be a thiol-based kinase sensing redox changes and forming an archaeal multicomponent system with the regulators MsrG/F/C.