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NikR–operator complex structure and the mechanism of repressor activation by metal ions
Eric R. Schreiter*,
Sheila C. Wang,
Deborah B. Zamble, and
Catherine L. Drennan*,
*Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; and Department of Chemistry, University of Toronto, Toronto, ON, Canada M5S 3H6
Communicated by Robert T. Sauer, Massachusetts Institute of Technology, Cambridge, MA, July 24, 2006
Received for publication December 22, 2005.
Abstract:
Metal ion homeostasis is critical to the survival of all cells.Regulation of nickel concentrations in Escherichia coli is mediatedby the NikR repressor via nickel-induced transcriptional repressionof the nickel ABC-type transporter, NikABCDE. Here, we reporttwo crystal structures of nickel-activated E. coli NikR, theisolated repressor at 2.1 Å resolution and in a complexwith its operator DNA sequence from the nik promoter at 3.1Å resolution. Along with the previously published structureof apo-NikR, these structures allow us to evaluate functionalproposals for how metal ions activate NikR, delineate the drasticconformational changes required for operator recognition, anddescribe the formation of a second metal-binding site in thepresence of DNA. They also provide a rare set of structuralviews of a ligand-responsive transcription factor in the unbound,ligand-induced, and DNA-bound states, establishing a model systemfor the study of ligand-mediated effects on transcription factorfunction.
Author contributions: E.R.S. and C.L.D. designed research; E.R.S.and S.C.W. performed research; E.R.S., S.C.W., D.B.Z., and C.L.D.analyzed data; and E.R.S., S.C.W., D.B.Z., and C.L.D. wrotethe paper.
Conflict of interest statement: No conflicts declared.
Data deposition: The atomic coordinates and structure factorsfor crystal structures of Ni-NikR and its complex with operatorDNA have been deposited in the Protein Data Bank, www.pdb.org(PDB ID codes 2HZA and 2HZV, respectively).
To whom correspondence should be addressed. E-mail: cdrennan{at}mit.edu
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