The AcrR protein represses transcription of the acrAB operon which encodes the periplasmic membrane fusion protein AcrA and the multidrug efflux pump AcrB. AcrB is a multidrug transporter that belongs to the resistance-nodulation-division (RND) superfamily of MDR pumps. AcrB possesses a wide range of ligand recognition, including most of the currently administered antibiotics, chemotherapeutic agents, bile salts, dyes, and detergents. AcrB functions in conjunction with AcrA and TolC, the outer membrane channel protein.
The AcrR N-terminal sequence shares similarity to the TetR family of transcriptional repressors. Like other members in this family, the N-terminal domain of AcrR contains a predicted DNA-binding helix-turn-helix (HTH) motif. The C-terminal domain has unique sequences and is expected to form a multi-drug binding site for its inducing drugs. Recent studies indicate that AcrR interacts with the same set of antimicrobial agents as AcrB with similar affinities. Binding a drug to the C-terminal ligand-binding domain of AcrR presumably triggers conformational change in its N-terminal DNA-binding region. This change results in the release of AcrR from its operator DNA, and thus allows transcription from its cognate promoter.