Figure 1. A two-component signal transduction paradigm. The level of phosphorylated response regulator (RR) is controlled through stimulus-induced conformational changes in the histidine kinase (HK), which alter its enzymatic activities. A membrane-localized HK with both kinase and phosphatase activities is shown here.

Figure 2. A two-component phosphorelay. As with a typical two-component system signalling is initiated through passage of phosphate from ATP to the conserved histidine of a HK. In this example, a membrane-localized HK with an extracytoplasmic input domain is shown. From the HK phosphate is transferred to a single domain RR containing only a receiver domain and then to a HPt protein. Ultimately, phosphate from the conserved histidine of the HPt protein is passed to the receiver domain of the final effector RR. This phosphorylation event alters a protein interaction face on the receiver domain, leading to activation of the output domain. In a phosphorelay, dephosphorylation of the phosphorylated receiver domains of the RRs by auxiliary phosphatases in response to separate stimuli allows for multiple points of response regulation.

Figure 3. Domain structure of HKs and RRs. (a) Domain structure of HKs. N, N-terminus; C, C-terminus. Grey ovals are transmembrane domains. Conserved sequence motifs in the catalytic domain are shown as lettered boxes. (b) Domain structure of RRs. D13, D57 and K109 represent the invariant residues found in the receiver domain, according to the position they are found in CheY. D, aspartate; K, lysine.