A tight tuneable range for Ni(II)-sensing and -buffering in cells

The metal-affinities of metal-sensing transcriptional regulators co-vary with cellular metal concentrations over more than 12 orders of magnitude. To understand the cause of this relationship, we determined the structure of the Ni(II)-sensor InrS then created cyanobacteria (Synechocystis PCC 6803) in which transcription of genes encoding a Ni(II)-exporter and a Ni(II)-importer were controlled by InrS variants with weaker Ni(II)-affinities. Variant strains were sensitive to elevated nickel and contained more nickel but the increase was small compared to the change in Ni(II)-affinity. All of the variant-sensors retained the allosteric mechanism which inhibits DNA binding upon metal binding but a response to nickel in vivo was only observed when the sensitivity was set to respond within a relatively narrow (less than 2 orders of magnitude) range of nickel-concentrations. The Ni(II)-affinity of InrS is attuned to cellular metal concentrations rather than the converse.