Bacteria are prone to various stressors so they need to sense and respond to these fluctuating conditions in order to survive. Two-component plays an important role in the bacterial kingdom to sense and adapt themselves to these varieties of stressors, for example oxidative stress, protein misfolding, nutrient starvation and many more. It is first described by Ninfa and Magasanik (1986) in the study of nitrogen starvation in Escherichia coli. Two-component system consists of a sensor histidine kinase and its cognate response regulator (Koretke,K.K. 2000). Sensor histidine kinase is bifunctional which means it can function as both kinase and phosphatase. It autophosphorylates itself upon sensing a signal, whereby the phosphoryl group from ATP molecule is transferred to a specific histine residue on the histidine kinase. It then acts as phosphodonor substrate for its cognate response regulator. The cognate response regulators is acting as phosphatase to the histidine kinase as it catalyses the transfer of the phosphoryl group from histidine kinase to its conserved aspartic acid residue. Once phosphorylated, response regulator undergoes conformational change which activates the output domain leading to either stimulation or repression of the targeted genes. As mentioned earlier on, histidine kinase protein also acts as phosphatase for its cognate response regulator if it is not stimulated to autophosphorylate.
This system has vast variations and the common variant is called the phosphorelay system which is a much more complex version of two-component system (Koretke,K.K. 2000). According to this system, its cognate response regulator is lacking an output domain. Hence, it needs to shuttle the phosphoryl group to a histidine phosphotransferase and eventually to a terminal response regulator which can then mediates an appropriate response. In some phosphorelay system, single polypeptide can be formed by the fusion of the response regulator lacking the output domain and C terminus of the histidine kinase. The phosphorelay system has been suggested to provide multiple control targets, thus allowing the integration of several of signals. The regulation two-component system works and examples of responses to different stressors will be discussed in more details in this paper
The Two-Component System and Different Stressors
Most histidine kinases are integral membrane proteins that sense signals through their periplasmic domain. Some histidine kinases can also be entirely cytoplasmic by which the sensing of stress signals is through the upstream of their catalytic regions. Histidine kinases possess two conserved domains which are the phosphorylation site domain where the conserved histidine residue can be found and an ATP-binding kinase site domain which catalyses the autophosphorylation activity. Response regulators contain two domains which are receiver domain containing the conserved aspartate residue and effector domain which...