Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognitionMadoori, P. K., Agustiandari, H., Driessen, A. J. M. & Thunnissen, A-M. W. H., 21-Jan-2009, In : EMBO Journal. 28, 2, p. 156-166 11 p.
Research output: Contribution to journal › Article › Academic › peer-review
LmrR is a PadR-related transcriptional repressor that regulates the production of LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional regulation is presumed to follow a drug-sensitive induction mechanism involving the direct binding of transporter ligands to LmrR. Here, we present crystal structures of LmrR in an apo state and in two drug-bound states complexed with Hoechst 33342 and daunomycin. LmrR shows a common topology containing a typical beta-winged helix-turn-helix domain with an additional C-terminal helix involved in dimerization. Its dimeric organization is highly unusual with a flat-shaped hydrophobic pore at the dimer centre serving as a multidrug-binding site. The drugs bind in a similar manner with their aromatic rings sandwiched in between the indole groups of two dimer-related tryptophan residues. Multidrug recognition is facilitated by conformational plasticity and the absence of drug-specific hydrogen bonds. Combined analyses using site-directed mutagenesis, fluorescence-based drug binding and protein-DNA gel shift assays reveal an allosteric coupling between the multidrug- and DNA-binding sites of LmrR that most likely has a function in the induction mechanism.
|Number of pages||11|
|Publication status||Published - 21-Jan-2009|
- bacterial multidrug transcription factors, multidrug recognition, LmrR, PadR, protein structure, CRYSTAL-STRUCTURES, SEQUENCE ALIGNMENTS, LACTOCOCCUS-LACTIS, PROTEIN, TRANSPORTER, REFINEMENT, RESISTANCE, ACTIVATOR, EXPRESSION, REVEALS