CHAPTER 13: Nickel Regulation

Nickel ions are required to cofactor several microbial enzymes. Transcriptionally regulated import and export systems have evolved to control cytoplasmic nickel levels and match physiological need with metal availability. In cases where there is no physiological need, only export systems will be required. Several different regulatory mechanisms have been identified that control gene expression in response to nickel ions. These include metal-responsive transcriptional regulators, periplasmic sensors that transmit Ni status across the inner membrane, and the recently identified NiCo riboswitch, the first RNA-based Ni sensor. The abundance of structural and functional studies available for these regulators provide an understanding of how nickel ions are selectivity recognized in the complex cellular milieu. Coordination chemistries that favour stable nickel ion binding over other metal ions enable proteins to couple conformational change to the presence of the correct metal. Interestingly, Ni-import systems are regulated by proteins that use four-coordinate planar geometry while export system regulators, both protein and RNA, favour six-coordinate sites, and as a result are also responsive to cobalt ions. The protein based sensors all have tight affinities for Ni, suggesting that intracellular buffered levels are well below a single atom/compartment volume. However, this leads to the unresolved question of how nickel ions are trafficked to metalloenzyme active sites in the face of a pool of high-affinity regulatory sites.