MarR family transcription factors: dynamic variations on a common scaffold.

Members of the multiple antibiotic resistance regulator (MarR) family of transcription factors are critical for bacterial cells to respond to chemical signals and to convert such signals into changes in gene activity. Obligate dimers belonging to the winged helix-turn-helix protein family, they are critical for regulation of a variety of functions, including degradation of organic compounds and control of virulence gene expression. The conventional regulatory paradigm is based on a genomic locus in which the gene encoding the MarR protein is divergently oriented from a gene under its control; MarR binding to the intergenic region controls expression of both genes by changing the interaction of RNA polymerase with gene promoters. MarR protein oxidation or binding of a small molecule ligand adversely affects DNA binding, resulting in altered expression of the divergent genes. The generality of this simple paradigm, including the regulation of Escherichia coli MarR by direct binding of antibiotics, has been challenged by reports published in recent years. In addition, structural and biochemical analyses of ligand binding to numerous MarR homologs are converging to identify a shared ligand-binding "hot-spot". This review highlights recent research advances that point to shared features, yet at the same time highlights the remarkable flexibility with which members of this protein family implement responses to inducing signals. A more comprehensive understanding of protein function will pave the way towards the development of both antibacterial agents and biosensors that are based on MarR family proteins.