title: Genetic analysis, structural modeling, and direct coupling analysis suggest a mechanism for phosphate signaling in Escherichia coli.
abstract: 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.
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Gardner
authors.forename: Justin B
authors.initials: JB
authors.lastname: Miller
authors.forename: Tanner
authors.initials: T
authors.lastname: Dean
authors.forename: Tanner
authors.initials: T
authors.lastname: Robinson
authors.forename: McCall
authors.initials: M
authors.lastname: Erickson
authors.forename: Perry G
authors.initials: PG
authors.lastname: Ridge
authors.forename: William R
authors.initials: WR
authors.lastname: McCleary
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010710:Phosphates / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D010710:Phosphates; D014157:Transcription Factors; C050770:phoU protein, E coli; C061279:PhoR protein, Bacteria