Intradomain LexA rotation is a prerequisite for DNA binding specificity

FEBS Lett. 2007 Oct 16;581(25):4816-20. doi: 10.1016/j.febslet.2007.09.006. Epub 2007 Sep 14.

Abstract

In the absence of DNA damage the LexA protein represses the bacterial SOS system. We performed molecular dynamic simulations of two LexA dimers bound to operators. Our model predicted that rotation of the LexA DNA binding domain, with respect to the dimerised C-terminal domain, is required for selective DNA binding. To confirm the model, double and quadruple cysteine LexA mutants were engineered. Electrophoretic mobility-shift assay and surface plasmon resonance showed that disulfide bond formation between the introduced cysteine residues precluded LexA specific DNA binding due to blocked domain reorientation. Our model could provide the basis for novel drug design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Colicins / genetics
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Models, Molecular
  • Mutation
  • Operator Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • Rotation
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism

Substances

  • Bacterial Proteins
  • Colicins
  • DNA-Binding Proteins
  • LexA protein, Bacteria
  • Serine Endopeptidases