Bacterial metal-sensing proteins exemplified by ArsR–SmtB family repressors

Detecting deficiency and excess of different metal ions is fundamental for every organism. Our understanding of how metals are detected by bacteria is exceptionally well advanced, and multiple families of cytoplasmic DNA-binding, metal-sensing transcriptional regulators have been characterised(ArsR-SmtB, MerR, CsoR-RcnR, CopY, DtxR, Fur, NikR). Some of the sensors regulate a single gene while others act globally controlling transcription of regulons. They not only modulate the expression of genes directly associated with metal homeostasis, but can also alter metabolism to reduce the cellular demand for metals in short supply. Different representatives of each of the sensor families can regulate gene expression in response to different metals, and the residues that form the sensory metal-binding sites have been defined in a number of these proteins. Indeed, in the case of theArsR-SmtB family, multiple distinct metal-sensing motifs (and one non-metal-sensing motif) have been identified which correlate with the detection of different metals. This review summarises the different families of bacterial metal-sensing transcriptional regulators and discusses current knowledge regarding the mechanisms of metal-regulated gene expression and the structural features of sensory metal-binding sites focusing on the ArsR-SmtB family. In addition, recent progress in understanding the principles governing the ability of the sensors to detect specific metals within a cell and the coordination of the different sensors to control cellular metal levels is discussed.