Structure of CheA, a signal-transducing histidine kinase

Cell. 1999 Jan 8;96(1):131-41. doi: 10.1016/s0092-8674(00)80966-6.


Histidine kinases allow bacteria, plants, and fungi to sense and respond to their environment. The 2.6 A resolution crystal structure of Thermotoga maritima CheA (290-671) histidine kinase reveals a dimer where the functions of dimerization, ATP binding, and regulation are segregated into domains. The kinase domain is unlike Ser/Thr/Tyr kinases but resembles two ATPases, Gyrase B and Hsp90. Structural analogies within this superfamily suggest that the P1 domain of CheA provides the nucleophilic histidine and activating glutamate for phosphotransfer. The regulatory domain, which binds the homologous receptor-coupling protein CheW, topologically resembles two SH3 domains and provides different protein recognition surfaces at each end. The dimerization domain forms a central four-helix bundle about which the kinase and regulatory domains pivot on conserved hinges to modulate transphosphorylation. Different subunit conformations suggest that relative domain motions link receptor response to kinase activity.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Dimerization
  • Histidine Kinase
  • Hydrolysis
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Methyl-Accepting Chemotaxis Proteins
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Conformation*
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Thermotoga maritima / enzymology*


  • Bacterial Proteins
  • Membrane Proteins
  • Methyl-Accepting Chemotaxis Proteins
  • Protein Kinases
  • Histidine Kinase
  • Adenosine Triphosphatases