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Curr Opin Struct Biol. 2010 Dec;20(6):763-71. doi: 10.1016/ Epub 2010 Oct 13.

The mechanism of signal transduction by two-component systems.

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Instituto de Biomedicina de Valencia-Consejo Superior de Investigaciones Científicas (IBV-CSIC) and Centro de Investigaciones en Red de Enfermedades Raras (CIBERER-ISCIII), Jaume Roig 11, Valencia 46010, Spain.


Two-component systems, composed of a homodimeric histidine kinase (HK) and a response regulator (RR), are major signal transduction devices in bacteria. Typically the signal triggers HK autophosphorylation at one His residue, followed by phosphoryl transfer from the phospho-His to an Asp residue in the RR. Signal extinction frequently involves phospho-RR dephosphorylation by a phosphatase activity of the HK. Our understanding of these reactions and of the determinants of partner specificity among HK-RR couples has been greatly increased by recent crystal structures and biochemical experiments on HK-RR complexes. Cis-autophosphorylation (one subunit phosphorylates itself) occurs in some HKs while trans-autophosphorylation takes place in others. We review and integrate this new information, discuss the mechanism of the three reactions and propose a model for transmembrane signaling by these systems.

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