Molecular Microbiology of Heavy Metals

Volume 6 of the series Microbiology Monographs pp 37-71


Metalloregulators: Arbiters of Metal Sufficiency

  • John D. HelmannAffiliated withDepartment of Microbiology, Cornell University Email author 
  • , Sumarin SoonsangaAffiliated withDepartment of Microbiology, Cornell University
  • , Scott GabrielAffiliated withDepartment of Microbiology, Cornell University

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Metal homeostasis relies on the ability of metalloregulatory proteins to coordinate the expression of transport and storage functions. Metalloregulatory proteins can be divided into two major groups: those that regulate the uptake of essential metals (the Fur, DtxR/MntR, and NikR families) and those that regulate metal efflux and detoxification mechanisms (the ArsR/SmtB and MerR families). Within each metalloregulator protein family, there is a tremendous diversity in metal selectivity and the corresponding biological responses. The availability of at least one protein structure from each family is beginning to provide insights into the origins of metal selectivity. Biochemical measurements of metal ion selectivity and affinity provide a window into the ambient metal ion conditions within the cytosol: metalloregulators that sense nutrient metals must be poised to bind the metal ion once the essential functional sites are saturated, but before adventitious associations begin to interfere with cellular function. Similarly, sensors of metal ion excess, whether for non-essential toxic metals or nutrient metals, must respond to metals, at levels below those that will inhibit or prevent cell growth, to activate appropriate defensive measures. Recent insights highlight the global nature of stress responses elicited by metal ion deficiency. In addition to the expected derepression of high affinity uptake systems, metal ion starvation leads to a large-scale remodeling of the proteome that includes: (i) metal-sparing, (ii) metal-substitution, and (iii) metal-mobilization responses.