Bicarbonate-mediated stimulation of RegA, the global virulence regulator from Citrobacter rodentium.

Abstract

The global virulence regulatory protein RegA, an AraC-like regulator, controls the expression of more than 60 genes in the mouse enteric pathogen Citrobacter rodentium. In the presence of bicarbonate, RegA activates the transcription of a number of virulence determinants and inhibits the expression of a series of housekeeping genes. To elucidate the molecular mechanism by which bicarbonate stimulates RegA activity, we carried out biophysical and mutational analyses. Our data indicate that RegA exists as a dimer in solution regardless of bicarbonate concentration. A leucine zipper, located in the region downstream of the N-terminal domain, is responsible for dimerisation. The N-terminal arm itself is involved in modulating the response to bicarbonate, which appears to bind to a region comprising a series of beta-sheets within the N-terminal domain. The presence of bicarbonate relieves the autoinhibition of RegA activity by its N-terminal arm. RegA is the first example of a bacterial virulence regulator that utilises the light switch mechanism, previously described for the Escherichia coli AraC protein, to respond to a gut-associated effector that controls its activity.

DOI: 10.1016/j.jmb.2009.10.033
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@article{Yang2009BicarbonatemediatedSO, title={Bicarbonate-mediated stimulation of RegA, the global virulence regulator from Citrobacter rodentium.}, author={Ji Yang and Con Dogovski and Dianna M. Hocking and Marija Tauschek and Matt Perugini and Roy Michael Robins-Browne}, journal={Journal of molecular biology}, year={2009}, volume={394 4}, pages={591-9} }