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Concept
Two-component regulatory system
Summary
In the field of molecular biology, a two-component regulatory system serves as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions. Two-component systems typically consist of a membrane-bound histidine kinase that senses a specific environmental stimulus and a corresponding response regulator that mediates the cellular response, mostly through differential expression of target genes. Although two-component signaling systems are found in all domains of life, they are most common by far in bacteria, particularly in Gram-negative and cyanobacteria; both histidine kinases and response regulators are among the largest gene families in bacteria. They are much less common in archaea and eukaryotes; although they do appear in yeasts, filamentous fungi, and slime molds, and are common in plants, two-component systems have been described as "conspicuously absent" from animals.
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 HWE and 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 regulator's receiver domain. This typically triggers a conformational change that activates the RR's effector domain, which in turn produces the cellular response to the signal, usually by stimulating (or repressing) expression of target genes.
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