Mechanisms of copper homeostasis in bacteria

Abstract

Copper is an important micronutrient required as a redox co-factor in the catalytic centers of enzymes. However, free copper is a potential hazard because of its high chemical reactivity. Consequently, organisms exert a tight control on Cu(+) transport (entry-exit) and traffic through different compartments, ensuring the homeostasis required for cuproprotein synthesis and prevention of toxic effects. Recent studies based on biochemical, bioinformatics, and metalloproteomics approaches, reveal a highly regulated system of transcriptional regulators, soluble chaperones, membrane transporters, and target cuproproteins distributed in the various bacterial compartments. As a result, new questions have emerged regarding the diversity and apparent redundancies of these components, their irregular presence in different organisms, functional interactions, and resulting system architectures.

Keywords: Cu+-ATPases; copper; homeostasis; metallochaperones; metalloenzymes; transmembrane transport.

Figure 1

Scheme of systems participating in Cu⁺ homeostasis in a Gram-negative bacterial cell. The drawing represents the major systems, and not all cuproenzymes are depicted. Various bacteria contain different subsets of these molecules (Hernández-Montes et al., 2012). Experimentally verified Cu⁺ transfer and transport events are indicated with solid lines. Postulated Cu⁺ fluxes are indicated with dotted lines. The colored shapes represent groups of proteins (various transcriptional regulators, various chaperones, etc.): putative outer membrane transporters (lavender), periplasmic Cu⁺ chaperones and cuproenzymes (green), membrane cuproenzymes (magenta), Cus system (royal blue), inner membrane transporters (purple), transcriptional regulators (red), cytosolic Cu⁺ chaperones (orange).

Figure 2

Structures and interaction between cytosolic Cu⁺-chaperones and Cu⁺-ATPases. Archeoglobus fulgidus C-terminal Cu⁺ binding domain of CopZ modeled using Enterococcus hirae CopZ (Protein Data Bank code 1CPZ) in light blue. A. fulgidus CopA modeled using Legionella pneumophila CopA (Protein Data Bank code 3RFU) as a template. The transmembrane segments (TM) are in gray, the electropositive platform helix is highlighted in green, the Cu⁺ entrance site aminoacids are in yellow, the transmembrane metal binding sites (TM-MBS) in dark blue, the actuator (A) domain in orange, the nucleotide (N) binding and (P) phosphorylation domain in red.