Comparison of the Pseudomonas aeruginosa and Escherichia coli PhoQ sensor domains - Evidence for distinct mechanisms of signal detection

The PhoP-PhoQ two-component system is present in a number of Gram-negative bacteria where it has roles in Mg2+ homeostasis and virulence. PhoQ is a tr ansmembrane histidine kinase that activates PhoP-mediated regulation of a s et of genes when the extracellular concentration of divalent cations is low . Divalent cations are thought to interact directly with the periplasmic Ph oQ sensor domain. The PhoP-PhoQ systems of Escherichia coli and Pseudomonas aeruginosa are similar in their biological response to extracellular dival ent cations; however, their sensor domains display little sequence identity . Here we have begun to explore the consequences of this sequence divergenc e by comparing the biophysical properties of the P. aeruginosa PhoQ sensor domain with the corresponding E. coli sensor domain. Unlike the E. coli pro tein, the P. aeruginosa PhoQ sensor domain undergoes changes in the circula r dichroism and fluorescence spectra as well as destabilization of its dime ric form in response to divalent cations. These results suggest that distin ct mechanisms of signal detection are utilized by these proteins. A hybrid protein in which the E. coli sensor domain has been substituted with the co rresponding P. aeruginosa sensor domain responds normally to the presence o f extracellular divalent cations in vivo in E. coli. Thus, despite apparent differences in the structural response to its stimulus, the P. aeruginosa sensor domain transduces signals to the E. coli PhoQ cytoplasmic kinase dom ain in a manner that mimics normal E. coli PhoQ function.