Complexity in ‘2-component’ signal transduction systems

The prototypical (Class I) sensory histidine kinase is comprised of a ligand binding domain coupled to an autokinase domain (Figure 1A). Ligand binding causes activation of the catalytic autokinase domain which hydrolyses ATP and autophosphorylates a conserved histidine residue located in a sub-domain of the histidine kinase. Transfer of this high energy phosphoryl group to a conserved aspartate residue in the receiver (REC) domain of the cognate response regulator protein causes a conformational change that results in activation (or relief of inhibition) of the output domain of the response regulator (Figure 1A) 1-3.