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PNAS 103 (37): 13676-13681

Copyright © 2006 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / BIOCHEMISTRY

NikR–operator complex structure and the mechanism of repressor activation by metal ions

Eric R. Schreiter*, Sheila C. Wang{dagger}, Deborah B. Zamble{dagger}, and Catherine L. Drennan*,{ddagger}

*Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; and {dagger}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 mediated by the NikR repressor via nickel-induced transcriptional repression of the nickel ABC-type transporter, NikABCDE. Here, we report two crystal structures of nickel-activated E. coli NikR, the isolated repressor at 2.1 Å resolution and in a complex with its operator DNA sequence from the nik promoter at 3.1 Å resolution. Along with the previously published structure of apo-NikR, these structures allow us to evaluate functional proposals for how metal ions activate NikR, delineate the drastic conformational changes required for operator recognition, and describe the formation of a second metal-binding site in the presence of DNA. They also provide a rare set of structural views of a ligand-responsive transcription factor in the unbound, ligand-induced, and DNA-bound states, establishing a model system for the study of ligand-mediated effects on transcription factor function.

Key Words: crystallography • DNA complex • nickel • transcription factor • metalloregulator


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. wrote the paper.

Conflict of interest statement: No conflicts declared.

Data deposition: The atomic coordinates and structure factors for crystal structures of Ni-NikR and its complex with operator DNA have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 2HZA and 2HZV, respectively).

{ddagger}To whom correspondence should be addressed. E-mail: cdrennan{at}mit.edu

© 2006 by The National Academy of Sciences of the USA


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