IcaR is a member of the tetracycline repressor (TetR) family, a collection of transcriptional repressors found in a wide variety of bacteria. The TetR family is named after a member that regulates expression of tetracycline resistance genes, but other TetR proteins have been shown to control a great number of pathways, such as antibiotic biosynthesis and response to osmotic stress. IcaR is believed to be involved in the regulation of biofilm production. Biofilms are complex assemblies of single celled organisms that can be formed under a variety of conditions. Bacteria in biofilms demonstrate enhanced antibiotic resistance, which makes them of particular interest.
IcaR is an orthogonal bundle of alpha helices that binds to DNA as a homodimer. The DNA binding region is a conserved helix-turn-helix that is rich in aromatic and positively charged residues. Two copies of the homodimer are found in the asymmetric unit and have a nearly identical quaternary arrangement. IcaR has been previously solved in Staphylococcus epidermidis (2ZCN). As expected from 65% sequence identity and 1.2Å RMSD, the structure of IcaR from S. epidermidis and S. aureus are extremely similar. The region distal to the DNA binding motif is better ordered in the current structure and could be completely visualized, although there is no secondary structure present. Other structural examples from the TetR family include proteins from Haloarcula marismortui (3CRJ) and Thermotoga maritime (2ID6).
Ramos,J.L., Martinez-Bueno,M., Molina-Henares,A.J., Teran,W., Watanabe,K., Zhang,X., Gallegos,M.T., Brennan,R. and Tobes,R. (2005) The TetR family of transcriptional repressors. Microbiol. Mol. Biol. Rev. 69: 326–356.
Jeng, W.Y., Ko, T.P., Liu, C.I., Guo, R.T., Liu, C.L., Shr, H.L., Wang, A.H.J. (2008) Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in Staphylococcus epidermidis Nucleic Acids Res. 36: 1567-1577