Nucleic Acids Research Advance Access originally published online on January 21, 2008
Nucleic Acids Research 2008 36(5):1567-1577; doi:10.1093/nar/gkm1176
Nucleic Acids Research, 2008, Vol. 36, No. 5 1567-1577
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in Staphylococcus epidermidis
1Institute of Biological Chemistry, 2National Core Facility of High-Throughput Protein Crystallography, 3Taiwan International Graduate Program, Academia Sinica, Taipei 115, 4Institute of Biochemical Sciences, 5Department of Life Sciences, National Taiwan University, Taipei 106 and 6Structural Biology Program, Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan
*To whom correspondence should be addressed. Tel: +886 2 27881981; Fax: +886 2 27882043; Email: ahjwang{at}gate.sinica.edu.tw
Received August 6, 2007. Revised December 25, 2007. Accepted December 26, 2007.
Expression of the gene cluster icaADBC is necessary for biofilm production in Staphylococcus epidermidis. The ica operon is negatively controlled by the repressor IcaR. Here, the crystal structure of IcaR was determined and the refined structure revealed a homodimer comprising entirely 
-helices, typical of the tetracycline repressor protein family for gene regulations. The N-terminal domain contains a conserved helix-turn-helix DNA-binding motif with some conformational variations, indicating flexibility in this region. The C-terminal domain shows a complementary surface charge distribution about the dyad axis, ideal for efficient and specific dimer formation. The results of the electrophoretic mobility shift assay and isothermal titration calorimetry suggested that a 28 bp core segment of the ica operator is implicated in the cooperative binding of two IcaR dimers on opposite sides of the duplex DNA. Computer modeling based on the known DNA-complex structure of QacR and site-specific mutagenesis experiments showed that direct protein–DNA interactions are mostly conserved, but with slight variations for recognizing the different sequences. By interfering with the binding of IcaR to DNA, aminoglycoside gentamicin and other antibiotics may activate the icaADBC genes and elicit biofilm production in S. epidermidis, and likely S. aureus, as a defense mechanism.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.