Locus of enterocyte effacement-encoded regulator (Ler) of pathogenic Escherichia coli competes off histone-like nucleoid-structuring protein (H-NS) through noncooperative DNA binding

J Biol Chem. 2014 May 16;289(20):13739-50. doi: 10.1074/jbc.M113.545954. Epub 2014 Mar 25.

Abstract

The locus of enterocyte effacement-encoded regulator (Ler) of enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) functions to activate transcription of virulence genes silenced by the histone-like nucleoid-structuring protein (H-NS). Despite its important role in the bacterial gene regulation, the binding mode of Ler to DNA and its mechanism in alleviating genes repressed by H-NS are largely unknown. In this study, we use magnetic tweezers to demonstrate that Ler binds extended DNA through a largely noncooperative process, which results in DNA stiffening and DNA folding depending on protein concentration. We also show that Ler can replace prebound H-NS on DNA over a range of potassium and magnesium concentrations. Our findings reveal the DNA binding properties of Ler and shed light to further understand the anti-silencing activity of Ler.

Keywords: Atomic Force Microscopy; DNA-binding Protein; Gene Regulation; H-NS; Ler; Magnetic Tweezers; Protein-DNA Interaction; Single Molecule Biophysics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Binding, Competitive*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Enterohemorrhagic Escherichia coli / genetics
  • Enterohemorrhagic Escherichia coli / metabolism*
  • Enteropathogenic Escherichia coli / genetics
  • Enteropathogenic Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism*
  • Hydrogen-Ion Concentration
  • Magnesium Chloride / pharmacology
  • Nucleic Acid Conformation
  • Potassium Chloride / pharmacology
  • Protein Binding / drug effects
  • Substrate Specificity
  • Temperature
  • Trans-Activators / metabolism*

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • H-NS protein, bacteria
  • Ler protein, E coli
  • Trans-Activators
  • Magnesium Chloride
  • Potassium Chloride