MzrA: a novel modulator of the EnvZ/OmpR two-component regulon

Mol Microbiol. 2009 Jun;72(6):1408-22. doi: 10.1111/j.1365-2958.2009.06728.x. Epub 2009 May 8.


Analysis of suppressors that alleviate the acute envelope stress phenotype of a DeltabamB DeltadegP strain of Escherichia coli identified a novel protein MzrA and pleiotropic envZ mutations. Genetic evidence shows that overexpression of MzrA--formerly known as YqjB and EcfM--modulates the activity of EnvZ/OmpR similarly to pleiotropic EnvZ mutants and alter porin expression. However, porin expression in strains devoid of MzrA or overexpressing it is still sensitive to medium osmolarity, pH and procaine, all of which modulate EnvZ/OmpR activities. Thus, MzrA appears to alter the output of the EnvZ/OmpR system but not its ability to receive and respond to various environmental signals. Localization and topology experiments indicate that MzrA is a type II membrane protein, with its N-terminus exposed in the cytoplasm and C-terminus in the periplasm. Bacterial two-hybrid experiments determined that MzrA specifically interacts with EnvZ but not with OmpR or the related membrane sensor kinase, CpxA. This and additional genetic and biochemical evidence suggest that the interaction of MzrA with EnvZ would either enhance EnvZ's kinase activity or reduce its phosphatase activity, thus elevating the steady state levels of OmpR approximately P. Furthermore, our data show that MzrA links the two-component envelope stress response regulators, CpxA/CpxR and EnvZ/OmpR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • DNA, Bacterial / genetics
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Expression Regulation, Bacterial
  • Genes, Regulator
  • Hydrogen-Ion Concentration
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Osmolar Concentration
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Porins / metabolism
  • Procaine / pharmacology
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Regulon
  • Substrate Specificity
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • Porins
  • Trans-Activators
  • osmolarity response regulator proteins
  • Procaine
  • Protein Kinases
  • envZ protein, E coli
  • Phosphoprotein Phosphatases