text: Two-component systems accomplish signal transduction through the phosphorylation of a response regulator (RR) by a histidine kinase (HK). Histidine kinases are typically homodimeric transmembrane proteins containing a histidine phosphotransfer domain and an ATP binding domain, though there are reported examples of histidine kinases in the atypical [http://pfam.xfam.org/family/PF07536 HWE] and [http://pfam.xfam.org/family/PF07568 HisKA2] families that are not homodimers. Response regulators may consist only of a receiver domain, but usually are multi-domain proteins with a receiver domain and at least one effector or output domain, often involved in DNA binding. Upon detecting a particular change in the extracellular environment, the HK performs an autophosphorylation reaction, transferring a phosphoryl group from adenosine triphosphate (ATP) to a specific histidine residue. The cognate response regulator (RR) then catalyzes the transfer of the phosphoryl group to an aspartate residue on the response regulators receiver domain. This typically triggers a conformational change that activates the RRs effector domain, which in turn produces the cellular response to the signal, usually by stimulating (or repressing) expression of target genes.
  Many HKs are bifunctional and possess phosphatase activity against their cognate response regulators, so that their signaling output reflects a balance between their kinase and phosphatase activities. Many response regulators also auto-dephosphorylate, and the relatively labile phosphoaspartate can also be hydrolyzed non-enzymatically. The overall level of phosphorylation of the response regulator ultimately controls its activity.