NikR-Operator Complex Structure and the Mechanism of Repressor Activation by Metal Ions

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-09, Vol.103 (37), p.13676-13681
• Main Authors: Schreiter, Eric R., Wang, Sheila C., Zamble, Deborah B., Drennan, Catherine L.
• Format: Article
• Language: English
• Subjects: ABC transporters; Amino Acid Sequence; Atoms; Base Sequence; Binding Sites; Biological Sciences; Crystal structure; Crystallography; Crystals; Deoxyribonucleic acid; DNA; E coli; Escherichia coli; Escherichia coli Proteins - agonists; Escherichia coli Proteins - chemistry; Ligands; Metal ions; Molecular Sequence Data; Molecules; Nickel; Nickel - chemistry; Operator Regions, Genetic; Phosphates; Potassium; Protein Conformation; Repressor Proteins - agonists; Repressor Proteins - chemistry; Transcription factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0606247103

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.