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Evolution and diversity of periplasmic proteins involved in copper homeostasis in gamma proteobacteria

Georgina Hernández-Montes1, José M Argüello2 and Brenda Valderrama1*

Author Affiliations

1 Departamento de Medicina Molecular y Bioprocesos. Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001 Col. Chamilpa, Cuernavaca, Mor, CP 62210, México

2 Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Gateway Park, 60 Prescott St, Worcester, MA, 01605, USA

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BMC Microbiology 2012, 12:249  doi:10.1186/1471-2180-12-249

Published: 2 November 2012



Different systems contributing to copper homeostasis in bacteria have been described in recent years involving periplasmic and transport proteins that provide resistance via metal efflux to the extracellular media (CopA/Cue, Cus, Cut, and Pco). The participation of these proteins in the assembly of membrane, periplasmic and secreted cuproproteins has also been postulated. The integration and interrelation of these systems and their apparent redundancies are less clear since they have been studied in alternative systems. Based on the idea that cellular copper is not free but rather it is transferred via protein-protein interactions, we hypothesized that systems would coevolve and be constituted by set numbers of essential components.


By the use of a phylogenomic approach we identified the distribution of 14 proteins previously characterized as members of homeostasis systems in the genomes of 268 gamma proteobacteria. Only 3% of the genomes presented the complete systems and 5% of them, all intracellular parasites, lacked the 14 genes. Surprisingly, copper homeostatic pathways did not behave as evolutionary units with particular species assembling different combinations of basic functions. The most frequent functions, and probably because of its distribution the most vital, were copper extrusion from the cytoplasm to the periplasm performed by CopA and copper export from the cytoplasm to the extracellular space performed by CusC, which along with the remaining 12 proteins, assemble in nine different functional repertoires.


These observations suggest complex evolutionary dynamics and still unexplored interactions to achieve copper homeostasis, challenging some of the molecular transport mechanism proposed for these systems.

Copper homeostasis; Gamma-proteobacteria; Evolution