Protein histidine kinases: assembly of active sites and their regulation in signaling pathways

Abstract

Protein histidine kinases (PHKs) function in Two Component Signaling pathways utilized extensively by bacteria and archaea. Many PHKs participate in three distinct, but interrelated signaling reactions: autophoshorylation, phosphotransfer (to a partner Response Regulator (RR) protein), and dephosphorylation of this RR. Detailed biochemical and structural characterization of several PHKs has revealed how the domains of these proteins can interact to assemble the three active sites that promote the necessary chemistry and how these domain interactions might be regulated in response to sensory input: the relative orientation of helices in the PHK dimerization domain can reorient, via cogwheeling (rotation) and kinking (bending), to effect changes in PHK activities that probably involve sequestration/release of the PHK catalytic domain by the dimerization domain.