title: NikR-operator complex structure and the mechanism of repressor activation by metal ions.
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 A resolution and in a complex with its operator DNA sequence from the nik promoter at 3.1 A 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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Schreiter
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Wang
authors.forename: Deborah B
authors.initials: DB
authors.lastname: Zamble
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003461:Crystallography; D029968:Escherichia coli Proteins / Q000819:agonists* / Q000737:chemistry*; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry*; D009875:Operator Regions, Genetic; D011487:Protein Conformation; D012097:Repressor Proteins / Q000819:agonists* / Q000737:chemistry*
chemical_list: D029968:Escherichia coli Proteins; C402409:NikR protein, E coli; D012097:Repressor Proteins; D009532:Nickel