Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins.
The MarR (multiple antibiotic resistance regulator) family of prokaryotic transcriptional regulators includes proteins critical for control of virulence factor production, bacterial response to antibiotic and oxidative stresses and catabolism of environmental aromatic compounds. Recognition of the adaptive cellular responses mediated by MarR homologs, and the clinical isolation of antibiotic-resistant bacterial strains harboring MarR mutations, has garnered increasing medical and agricultural attention to this family. MarR proteins exist as homodimers in both free and DNA-bound states. Sequence specific DNA-binding to palindromic or pseudopalindromic sites is mediated by a conserved winged helix fold and, for numerous homologs, this association is attenuated by specific anionic lipophilic ligands. The mechanism of ligand-mediated allosteric control of DNA binding is unique amongst prokaryotic transcriptional regulators in that the DNA- and ligand-binding domains almost completely overlap in the residues involved. Until recently, our understanding of ligand-binding has been limited to a MarR-salicylate co-crystal structure, with little information on the allosteric mechanisms linking ligand-recognition and DNA-binding. However, recent biochemical and biophysical data on MarR homologs have begun to resolve the mechanisms by which these proteins mediate ligand-responsive transcriptional control.
Wilkinson
Steven P
SP
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Grove
Anne
A
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics*
D029968:Escherichia coli Proteins; D008024:Ligands; C080004:MarR protein, E coli; D012097:Repressor Proteins