Conformational equilibrium defines the variable induction of the multidrug-binding transcriptional repressor QacR

Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19963-19972. doi: 10.1073/pnas.1906129116. Epub 2019 Sep 16.


QacR, a multidrug-binding transcriptional repressor in pathogenic bacteria Staphylococcus aureus, modulates the transcriptional level of the multidrug transporter gene, qacA, in response to engaging a set of diverse ligands. However, the structural basis that defines the variable induction level remains unknown. Here, we reveal that the conformational equilibrium between the repressive and inducive conformations in QacR defines the induction level of the transporter gene. In addition, the unligated QacR is already partly populated in the inducive conformation, allowing the basal expression of the transporter. We also showed that, in the known constitutively active QacR mutants, the equilibrium is shifted more toward the inducive conformation, even in the unligated state. These results highlight the unexpected structural mechanism, connecting the promiscuous multidrug binding to the variable transcriptional regulation of QacR, which provide clues to dysfunctioning of the multidrug resistance systems.

Keywords: NMR; dynamics; multidrug resistance; structure; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Calorimetry
  • Drug Resistance, Multiple, Bacterial*
  • Gene Expression Regulation, Bacterial*
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Membrane Transport Proteins / metabolism*
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Repressor Proteins / metabolism*
  • Staphylococcus aureus / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic


  • Bacterial Proteins
  • Ligands
  • Membrane Transport Proteins
  • QacR protein, Staphylococcus aureus
  • Repressor Proteins
  • Transcription Factors