Histidine kinases: diversity of domain organization

Mol Microbiol. 1999 Nov;34(4):633-40. doi: 10.1046/j.1365-2958.1999.01646.x.


Histidine kinases play a major role in signal transduction in prokaryotes for the cellular adaptation to environmental conditions and stresses. Recent progress in the three-dimensional structure determination of two representative members of histidine kinases, EnvZ (class I) and CheA (class II), has revealed common structural features, as well as a kinase catalytic motif topologically similar to those of the ATP-binding domains of a few ATPases. They have also disclosed that there are significant differences in domain organization between class I and II histidine kinases, possibly reflecting their distinct locations, functions and regulatory mechanisms. In spite of this diversity, both class I and II histidine kinases use similar four-helix bundle motifs to relay phosphoryl groups from ATP to regulatory domains of response regulators. The previously known so-called transmitter domain of histidine kinase is further dissected into two domains: a CA (Catalytic ATP-binding) domain and a DHp (Dimerization Histidine phosphotransfer) domain for class I, or a CA domain and an HPt (Histidine-containing Phosphotransfer) domain for class II histidine kinases. From a comparative analysis of the CA domains of EnvZ, CheA and their ATPase homologues, the core elements of the CA domain have been derived. The apparent resemblance between DHp and HPt domains is only superficial, and significant differences between them are discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Bacteria / chemistry
  • Bacteria / enzymology
  • Binding Sites
  • Histidine Kinase
  • Models, Molecular
  • Phosphorylation
  • Protein Kinases / chemistry*
  • Protein Kinases / classification
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary
  • Signal Transduction


  • Adenosine Triphosphate
  • Protein Kinases
  • Histidine Kinase