TY - JOUR
T1 - Genetic analysis, structural modeling, and direct coupling analysis suggest a mechanism for phosphate signaling in Escherichia coli
AU - Gardner, Stewart G.
AU - Miller, Justin B.
AU - Dean, Tanner
AU - Robinson, Tanner
AU - Erickson, McCall
AU - Ridge, Perry G.
AU - McCleary, William R.
N1 - Publisher Copyright:
© 2015 Gardner et al.; licensee BioMed Central Ltd.
PY - 2015
Y1 - 2015
N2 - Background: Proper phosphate signaling is essential for robust growth of Escherichia coli and many other bacteria. The phosphate signal is mediated by a classic two component signal system composed of PhoR and PhoB. The PhoR histidine kinase is responsible for phosphorylating/dephosphorylating the response regulator, PhoB, which controls the expression of genes that aid growth in low phosphate conditions. The mechanism by which PhoR receives a signal of environmental phosphate levels has remained elusive. A transporter complex composed of the PstS, PstC, PstA, and PstB proteins as well as a negative regulator, PhoU, have been implicated in signaling environmental phosphate to PhoR. Results: This work confirms that PhoU and the PstSCAB complex are necessary for proper signaling of high environmental phosphate. Also, we identify residues important in PhoU/PhoR interaction with genetic analysis. Using protein modeling and docking methods, we show an interaction model that points to a potential mechanism for PhoU mediated signaling to PhoR to modify its activity. This model is tested with direct coupling analysis. Conclusions: These bioinformatics tools, in combination with genetic and biochemical analysis, help to identify and test a model for phosphate signaling and may be applicable to several other systems.
AB - Background: Proper phosphate signaling is essential for robust growth of Escherichia coli and many other bacteria. The phosphate signal is mediated by a classic two component signal system composed of PhoR and PhoB. The PhoR histidine kinase is responsible for phosphorylating/dephosphorylating the response regulator, PhoB, which controls the expression of genes that aid growth in low phosphate conditions. The mechanism by which PhoR receives a signal of environmental phosphate levels has remained elusive. A transporter complex composed of the PstS, PstC, PstA, and PstB proteins as well as a negative regulator, PhoU, have been implicated in signaling environmental phosphate to PhoR. Results: This work confirms that PhoU and the PstSCAB complex are necessary for proper signaling of high environmental phosphate. Also, we identify residues important in PhoU/PhoR interaction with genetic analysis. Using protein modeling and docking methods, we show an interaction model that points to a potential mechanism for PhoU mediated signaling to PhoR to modify its activity. This model is tested with direct coupling analysis. Conclusions: These bioinformatics tools, in combination with genetic and biochemical analysis, help to identify and test a model for phosphate signaling and may be applicable to several other systems.
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U2 - 10.1186/1471-2156-16-S2-S2
DO - 10.1186/1471-2156-16-S2-S2
M3 - Article
C2 - 25953406
AN - SCOPUS:84989172942
SN - 1471-2156
VL - 16
JO - BMC Genetics
JF - BMC Genetics
M1 - S2
ER -