Metal-dependent and metal-responsive regulatory systems
John D. Helmann
from: Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition (Edited by: Stephen Spiro and Ray Dixon). Caister Academic Press, U.K. (2010)
Metal ions play key roles in bacterial sensory systems as both cofactor and signal. Here, we distinguish between those sensors that require a metal ion for signal perception (metal-dependent sensors) and those for which the metal itself is the signal (metalloregulatory proteins). Metal-dependent sensors most commonly use either iron or zinc as cofactor. Iron-dependent, metal-dependent sensors figure prominently in pathways that orchestrate responses to reactive oxygen/nitrogen species. Examples include PerR, which senses hydrogen peroxide by metal-catalyzed protein oxidation, and NorR, which senses nitric oxide by nitrosylation of a non-heme iron atom. Zinc-dependent sensors often use reactive cysteine thiolates to sense reactive oxygen species (as in RsrA and Hsp33) or alkylating agents (Ada). Metalloregulatory proteins sense metal ions by their reversible interaction with specific sensory sites and, in response, coordinate appropriate transcriptional (and less commonly translational) responses. Nutrient metal ions commonly act as co-factors for transcriptional repressors and thereby repress uptake pathways. Conversely, toxic levels of metal ions will trigger derepression or activation of efflux or sequestration mechanisms. Here, we review the major families of metalloregulatory proteins and the general bioinorganic principles governing their function in the cytosol read more ...