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J Mol Biol. 2000 Jul 7;300(2):291-305.

Acetyl phosphate-dependent activation of a mutant PhoP response regulator that functions independently of its cognate sensor kinase.

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Howard Hughes Medical Institute, Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.


The two-component system is a signal communication network generally consisting of a sensor kinase that receives inputs from the environment and modifies the phosphorylated state of a response regulator that executes an adaptive behavior. PhoP is a response regulator that controls virulence gene expression in Salmonella enterica. Transcription of PhoP-regulated genes is modulated by the Mg(2+) levels detected by the sensor PhoQ. Here, we describe a PhoP mutant protein, PhoP*, that functions in the absence of its cognate sensor, thereby allowing transcription of PhoP-activated genes independently of the Mg(2+ )concentration in the environment. The PhoP* protein harbors a S93N substitution in the response regulator receiver domain. PhoP*-mediated transcription is abolished by either mutation of the aspartate residue that is conserved among response regulators as the site of phosphorylation or inactivation of the pta-encoded phosphotransacetylase. This enzyme mediates the production of acetyl phosphate, which has been shown to serve as a low molecular mass phosphate donor for certain response regulators. The purified PhoP* protein autophosphorylated from acetyl phosphate more efficiently than the wild-type PhoP protein in vitro. The PhoP* protein retained the capacity to interact with the PhoQ protein, which promoted phosphorylation of the PhoP* protein in vitro and abolished PhoP*-mediated transcription under high Mg(2+ )concentrations in vivo. Cumulatively, our results uncover a role of PhoQ in transcriptional repression during growth in millimolar Mg(2+ )and define a mutant response regulator form with an increased capacity to be phosphorylated by acetyl phosphate.

[Indexed for MEDLINE]

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