Article
- The EMBO Journal (2002) 21, 1210 - 1218
- doi:10.1093/emboj/21.5.1210
There is an Erratum (May 2002) associated with this Article.
Subject Categories:
Structural basis for cooperative DNA binding by two dimers of the multidrug-binding protein QacR
Maria A. Schumacher1, Marshall C. Miller1, Steve Grkovic2, Melissa H. Brown2, Ronald A. Skurray2 and Richard G. Brennan1
- Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97201-3098, USA
- School of Biological Sciences, A12, University of Sydney, Sydney, NSW 2006, Australia
Correspondence to:
Richard G. Brennan, E-mail: brennanr@ohsu.edu
Received 1 November 2001; Accepted 12 December 2001; Revised 10 December 2001
Abstract
The Staphylococcus aureus multidrug-binding protein QacR represses transcription of the qacA multidrug transporter gene and is induced by multiple structurally dissimilar drugs. QacR is a member of the TetR/CamR family of transcriptional regulators, which share highly homologous N-terminal DNA-binding domains connected to seemingly non-homologous ligand-binding domains. Unlike other TetR members, which bind 
15 bp operators, QacR recognizes an unusually long 28 bp operator, IR1, which it appears to bind cooperatively. To elucidate the DNA-binding mechanism of QacR, we determined the 2.90 Å resolution crystal structure of a QacR–IR1 complex. Strikingly, our data reveal that the DNA recognition mode of QacR is distinct from TetR and involves the binding of a pair of QacR dimers. In this unique binding mode, recognition at each IR1 half-site is mediated by a complement of DNA contacts made by two helix–turn–helix motifs. The inferred cooperativity does not arise from cross-dimer protein–protein contacts, but from the global undertwisting and major groove widening elicited by the binding of two QacR dimers.
Keywords:
- DNA binding cooperativity,
- multidrug-binding protein,
- protein–DNA complex,
- QacR,
- repressor
