Multiple strategies govern a layered zinc homeostasis in Cupriavidus metallidurans

Abstract

Zinc is an important micronutrient that sustains cellular biochemistry as a catalytic and structural cofactor in enzymes. For biological systems, maintenance of zinc homeostasis and availability is essential in order to ensure metalation of the requiring enzymes. Cupriavidus metallidurans, a model organism for bacterial metal homeostasis, maintains zinc homeostasis via a flow-equilibrium of zinc cations. This ensures correct metalation of enzymes and avoids mis-metalation by other competing transition metal cations in the cytosol. Furthermore, this bacterium substitutes cellular zinc with cobalt ions in zinc depletion. This forms an inextricable link between zinc and cobalt homeostasis controlled by four proteins. ZupT and DmeF mediate the import and export of these cations, and two metallochaperones of the COG0523 family, CobW2 and CobW3, are responsible for the cytoplasmic handling of zinc and cobalt. CoW2 acts as a metal storage protein, and CobW3 influences import of cobalt ions.