title: The small membrane protein MgrB regulates PhoQ bifunctionality to control PhoP target gene expression dynamics.
abstract: In Escherichia coli and other γ-proteobacteria, the PhoQ-PhoP two-component signaling system responds to low extracellular Mg++and cationic antimicrobial peptides. On transition to inducing conditions, the expression of PhoP-dependent genes increases rapidly, but then decays to a new, intermediate steady-state level, a phenomenon often referred to as partial adaptation. The molecular basis for this partial adaptation has been unclear. Here, using time-lapse fluorescence microscopy to examine PhoP-dependent gene expression in individual E. coli cells we show that partial adaptation arises through a negative feedback loop involving the small protein MgrB. When E. coli cells are shifted to low Mg++, PhoQ engages in multiple rounds of autophosphorylation and phosphotransfer to PhoP, which, in turn, drives the expression of mgrB. MgrB then feeds back to inhibit the kinase activity of PhoQ. PhoQ is bifunctional such that, when not active as a kinase, it can stimulate the dephosphorylation of PhoP. Thus, MgrB drives the inactivation of PhoP and the observed adaptation in PhoP-dependent gene expression. Our results clarify the source of feedback inhibition in the E. coli PhoQ-PhoP system and reveal how exogenous factors, such as MgrB, can combine with a canonical two-component signaling pathway to produce complex temporal dynamics in target gene expression.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Salazar
authors.affiliation: Merck Research Laboratories, Boston, MA, 02115, USA.
authors.forename: Anna I
authors.initials: AI
authors.lastname: Podgornaia
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. laub@mit.edu.|Howard Hughes Medical Institute, Cambridge, MA, 02139, USA. laub@mit.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Laub
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D008274:Magnesium / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C571543:MgrB protein, E coli; C465562:PhoP protein, E coli; C576029:PhoQ protein, E coli; D008274:Magnesium