Bacteria, such as Escherichia coli, have enzymes that require nickel ions, and they express a nickel transporter to acquire the metal from the environment. To keep cellular concentrations of nickel relatively constant, the expression of the transporter is regulated by a repressor, NikR, which is itself a nickel sensor. NikR binds to the operator of the transporter gene and represses transcription only when it is in the nickel-bound form. Schreiter et al. solved the crystal structures of the nickel-bound form of NikR from E. coli both alone and in a complex with a DNA fragment corresponding to the promoter of the nickel transporter gene. The protein has two DNA-binding domains that interact with sites in the palindromic operator on either side of a metal-binding domain (MBD). In other ligand-regulated transcription factors, activation is proposed to occur when a change in the spacing between the DNA-binding domains is altered such that they interact more effectively with the promoter DNA. Comparison of the new structures with the previously reported structure of nickel-free protein indicates that this is not how NikR works. The allosteric changes that occur when metal binds do not appear to put the DNA binding domains into position for interaction with the promoter. Rather, they appear to create a new interactive surface within the metal binding domain that enhances the interaction of the protein with the promoter DNA helix. Changes in the protein structure appear to generate a second metal binding site as well, which may decrease flexibility of the protein and hold it in a conformation that more efficiently binds DNA. The results provide a detailed look at the precise molecular changes that underlie transcriptional control by a ligand-regulated transcription factor.
E. R. Schreiter, S. C. Wang, D. B. Zamble, C. L. Drennan, NikR–operator complex structure and the mechanism of repressor activation by metal ions. Proc. Natl. Acad. Sci. U.S.A. 103, 13676-13681 (2006). [Abstract] [Full Text]