The mechanism of signal transduction by two-component systems

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytoplasm / metabolism
  • Histidine Kinase
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism
  • Signal Transduction*


  • Protein Kinases
  • Histidine Kinase
  • Phosphoric Monoester Hydrolases