Histidine kinases (HK) are transmembrane proteins found in two-component systems (TCS). HKs recognise a ligand or change extracellularly, causing an intracellular conformational change in the catalytic ATPase (CA), inducing a response in the response regulator (RR). The CA causes the activation of the RR, through the phosphorylation of a conserved histidine residue on the transmitter domain (DHP, dimerisation of the histidine that is then phosphorylated).
HK activation can lead to changes in bacterial cell physiology, such as changing the activity of regulons or specific genes, through the production of DNA-binding proteins.
Acid resistance in E. coli is controlled by a two-component system. The high extracellular concentration of protons is detected by the HK, suppressing the expression of an anti-sigma-38 factor, leading to the upregulation of acid-response genes. This response involves the EvgSA and PhoQP systems. Ensuring that acid-response genes are only expressed during cell stress is important, maintaining the specificity of the response. The acid response is important in allowing the E. coli to survive when exposed to low pH.