Maintaining Copper Homeostasis - Molecular Studies on Bacterial Copper Transporters

Abstract

Bacteria have evolved sophisticated cellular transport mechanisms to maintain metal homeostasis to not only utilize metals as important cofactors but also to evade the toxicity of these ions. The delicate balance is maintained by several homeostatic mechanisms that range from active cytoplasmic export, modification, sequestration, and periplasmic detoxification of toxic metals to the extracellular milieu. One mechanism involves active periplasmic extrusion of toxic substrates via a transmembrane spanning tripartite protein complex. The mechanism of substrate binding and subsequent efflux has yet to be elucidated. However, genetic, comparative genomic, biochemical, and functional analyses of the components of the heavy-metal efflux family have allowed the development of proposed models for a substrate transport pathway. The goals of this research were to identify the roles these systems play and to further characterize these systems on a molecular level to ultimately understand the mechanism of substrate transport. Elucidating a transport pathway in metal transporters allows for the development of a revised working model, which ultimately can have implications for antimicrobial drug development.