Coordination key to specificity in metal ion homeostasis

INOR 934

Sharon Leitch, sleitch@chem.umass.edu1, Jeffrey S. Iwig2, Michael J. Bradley2, Jessica L. Rowe2, Peter T. Chivers2, and Michael J Maroney, mmaroney@chem.umass.edu3. (1) Department of Chemistry, University of Massachusetts-Amherst, 710 N. Pleasant St., Amherst, MA 01069, (2) Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231 Rm 1905 S. Building, 4566 Scott Ave., St. Louis, MO 63110, (3) Department of Chemistry, University of Massachusetts, Amherst, 710 N. Pleasant St., Amherst, MA 01003
Metal ion homeostasis depends upon the presence of transcriptional regulators that respond specifically to the presence of a particular metal ion. Here, we compare two nickel-responsive transcriptional regulators from E. coli, NikR and RcnR for insights into how Nature designs a protein that elicits a response to Ni(II) ions and not to other transition metals, despite similar charges and ionic radii. The studies point to allosteric mechanisms, but differ in the details of how the metal identity is communicated to the protein structure. NikR is a nickel-responsive transcriptional repressor of the nikABCDE operon that encodes a nickel uptake permease. Although the metal binding affinity follows the Irving-Williams series, an in vivo assay shows repression is Ni(II) specific. XAS reveals that each metal adopts a unique structure that results in different conformations of the protein being favored. RcnR is a second regulatory protein responsible for derepression of the efflux protein RcnA upon Ni(II) and Co(II). In the case of RcnR, the interaction with the single cysteine residue appears to identify the metal; it is clearly a ligand of Co(II), but has a weak interaction with Ni(II).
 

Spectroscopy of Inorganic Systems
9:00 AM-11:20 AM, Thursday, August 23, 2007 BCEC -- 211, Oral

Division of Inorganic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007