The MarR Family of Transcriptional Regulators - A Structural Perspective

Abstract

All living organisms have molecular systems that enable them to resist a variety of toxic substances and environmental stresses. Proteins belonging to the Multiple antibiotic resistance Regulators (MarR) family reportedly regulate the expression of proteins conferring resistance to multiple antibiotics, organic solvents, household disinfectants, oxidative stress agents and pathogenic factors (Alekshun & Levy, 1999a; Miller & Sulavik, 1996; Aravind et al., 2005). The marR gene was initially identified as a component of the negative regulator encoded by the marRAB locus in Escherichia coli (George & Levy, 1983a, b). Currently, a large number of MarR-like proteins (~12,000) can be found in bacterial and archaeal domains, and the physiological role of around 100 of them have been characterized. Members of the MarR family of transcriptional regulatory proteins form a homodimer to bind to their cognate double-stranded DNA (dsDNA). The protein-DNA interactions is regulated by specific phenolic (lipophilic) compounds, such as salicylate, ethidium, carbonyl cyanide m-chlorophenylhydrazone (CCCP) and benzoate. The MarR homologues contain a winged helix-turn-helix (wHtH) motif at the DNA binding site, and this motif is well known for DNA binding in eukaryotes, prokaryotes, archaea and viruses. In this chapter, we will discuss the identification, three-dimensional structure and interactions with ligand (drug)/DNA of MarR family proteins.