Occurrence of Copper Proteins through the Three Domains of Life: A Bioinformatic Approach

Andreini, Claudia; Banci, Lucia; Bertini, Ivano; Rosato, Antonio

doi:10.1021/pr070480u

Cited by 184 publications

(154 citation statements)

References 58 publications

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“…S1), yet Ni-and Mo-binding structures are clearly more abundant in akaryotic relative to eukaryotic proteomes, although both only comprise a minuscule portion of most proteomes (Table S1). Cu-binding domains are in similar abundance in all three superkingdoms (Table S1), a result consistent with a previous survey conducted using sequence-based methods (22). Many akaryotic proteomes contain only one or no Cu-binding protein domains, preventing a robust estimation of a power-law slope, whereas eukaryotic proteomes exhibit a preferential accumulation of Cubinding domains with increasing proteome size ( Fig.…”

Section: Resultssupporting

confidence: 89%

History of biological metal utilization inferred through phylogenomic analysis of protein structures

Dupont

Butcher

Valas³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

275

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The fundamental chemistry of trace elements dictates the molecular speciation and reactivity both within cells and the environment at large. Using protein structure and comparative genomics, we elucidate several major influences this chemistry has had upon biology. All of life exhibits the same proteome size-dependent scaling for the number of metal-binding proteins within a proteome. This fundamental evolutionary constant shows that the selection of one element occurs at the exclusion of another, with the eschewal of Fe for Zn and Ca being a defining feature of eukaryotic proteomes. Early life lacked both the structures required to control intracellular metal concentrations and the metal-binding proteins that catalyze electron transport and redox transformations. The development of protein structures for metal homeostasis coincided with the emergence of metal-specific structures, which predominantly bound metals abundant in the Archean ocean. Potentially, this promoted the diversification of emerging lineages of Archaea and Bacteria through the establishment of biogeochemical cycles. In contrast, structures binding Cu and Zn evolved much later, providing further evidence that environmental availability influenced the selection of the elements. The late evolving Zn-binding proteins are fundamental to eukaryotic cellular biology, and Zn bioavailability may have been a limiting factor in eukaryotic evolution. The results presented here provide an evolutionary timeline based on genomic characteristics, and key hypotheses can be tested by alternative geochemical methods.Archean-Proterozoic | biogeochemistry | bioinorganic chemistry | evolution | metal homeostasis M etalloproteins contain one or more ions of an inorganic element in their 3D structure and are said to comprise 30% of all proteins (1). Many biological pathways contain at least one metalloenzyme (2) and consequently require Mg, K, Ca, Fe, Mn, and Zn to sustain life (3). Other elements, like Cu, Mo, Ni, Se, and Co, are required by many-though not all-organismal lineages, and the utilization of trace elements varies greatly between species (3). The different elements have a range of affinities for most coordinating environments in the order Mg +2 /Ca +2 < Mn +2 < Fe +2 < Co +2 < Ni +2 < Cu +2 ∼Zn +2 , an equilibrium series known as the Irving-Williams Series (4). This array of outer-sphere chemistry provides significant catalytic diversity, yet has consequences for both biological and environmental chemistry. Within the cell, metals compete for protein binding sites; hence, extensive protein networks involving transporters and metalsensing regulatory proteins are required to maintain the proper subcellular concentrations of each element, and in some cases directly shuttle each metal to its requisite metalloprotein in the proper cellular compartment (1, 5, 6). It has been hypothesized that the establishment of a metal homeostasis system is required for distinct phylotypes of cells to develop (7).Environmentally, for similar fundamental chemical reasons, the...

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Section: Resultssupporting

confidence: 89%

History of biological metal utilization inferred through phylogenomic analysis of protein structures

Dupont

Butcher

Valas³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

275

245

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“…Indeed, it is well known that the Cu(I) and Fe(III) ion species are highly competitive (64), and the selective influence of Cu(I), which is the predominant intracellular copper species (35), may further result from its natural preference for S donor ligands, while Cu(II) prefers N donors (2). The model of metal replacement at the ironsulfur cluster binding sites is also supported by the finding that cobalt stress also affects the function of iron-sulfur cluster proteins, including the IscU and SufA scaffolding components in E. coli (48).…”

Section: Discussionmentioning

confidence: 99%

Copper Stress Affects Iron Homeostasis by Destabilizing Iron-Sulfur Cluster Formation in Bacillus subtilis

et al. 2010

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Copper and iron are essential elements for cellular growth. Although bacteria have to overcome limitations of these metals by affine and selective uptake, excessive amounts of both metals are toxic for the cells. Here we investigated the influences of copper stress on iron homeostasis in Bacillus subtilis, and we present evidence that copper excess leads to imbalances of intracellular iron metabolism by disturbing assembly of iron-sulfur cofactors. Connections between copper and iron homeostasis were initially observed in microarray studies showing upregulation of Fur-dependent genes under conditions of copper excess. This effect was found to be relieved in a csoR mutant showing constitutive copper efflux. In contrast, stronger Fur-dependent gene induction was found in a copper efflux-deficient copA mutant. A significant induction of the PerR regulon was not observed under copper stress, indicating that oxidative stress did not play a major role under these conditions. Intracellular iron and copper quantification revealed that the total iron content was stable during different states of copper excess or efflux and hence that global iron limitation did not account for copperdependent Fur derepression. Strikingly, the microarray data for copper stress revealed a broad effect on the expression of genes coding for iron-sulfur cluster biogenesis (suf genes) and associated pathways such as cysteine biosynthesis and genes coding for iron-sulfur cluster proteins. Since these effects suggested an interaction of copper and iron-sulfur cluster maturation, a mutant with a conditional mutation of sufU, encoding the essential iron-sulfur scaffold protein in B. subtilis, was assayed for copper sensitivity, and its growth was found to be highly susceptible to copper stress. Further, different intracellular levels of SufU were found to influence the strength of Fur-dependent gene expression. By investigating the influence of copper on cluster-loaded SufU in vitro, Cu(I) was found to destabilize the scaffolded cluster at submicromolar concentrations. Thus, by interfering with iron-sulfur cluster formation, copper stress leads to enhanced expression of cluster scaffold and target proteins as well as iron and sulfur acquisition pathways, suggesting a possible feedback strategy to reestablish cluster biogenesis.

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“…any bacteria utilize copper as an essential cofactor for enzymes involved in electron transfer reactions, including superoxide dismutase, cytochrome c oxidase, and NADH dehydrogenase (1,2). Although it is required in low concentrations, copper at higher levels can pose a threat because of its high reactivity.…”

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confidence: 99%

The copYAZ Operon Functions in Copper Efflux, Biofilm Formation, Genetic Transformation, and Stress Tolerance in Streptococcus mutans

et al. 2015

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In bacteria, copper homeostasis is closely monitored to ensure proper cellular functions while avoiding cell damage. Most Gram-positive bacteria utilize the copYABZ operon for copper homeostasis, where copA and copB encode copper-transporting P-type ATPases, whereas copY and copZ regulate the expression of the cop operon. Streptococcus mutans is a biofilm-forming oral pathogen that harbors a putative copper-transporting copYAZ operon. Here, we characterized the role of copYAZ operon in the physiology of S. mutans and delineated the mechanisms of copper-induced toxicity in this bacterium. We observed that copper induced toxicity in S. mutans cells by generating oxidative stress and disrupting their membrane potential. Deletion of the copYAZ operon in S. mutans strain UA159 resulted in reduced cell viability under copper, acid, and oxidative stress relative to the viability of the wild type under these conditions. Furthermore, the ability of S. mutans to form biofilms and develop genetic competence was impaired under copper stress. Briefly, copper stress significantly reduced cell adherence and total biofilm biomass, concomitantly repressing the transcription of the gtfB, gtfC, gtfD, gbpB, and gbpC genes, whose products have roles in maintaining the structural and/or functional integrity of the S. mutans biofilm. Furthermore, supplementation with copper or loss of copYAZ resulted in significant reductions in transformability and in the transcription of competence-associated genes. Copper transport assays revealed that the ⌬copYAZ strain accrued significantly large amounts of intracellular copper compared with the amount of copper accumulation in the wild-type strain, thereby demonstrating a role for CopYAZ in the copper efflux of S. mutans. The complementation of the CopYAZ system restored copper expulsion, membrane potential, and stress tolerance in the copYAZ-null mutant. Taking these results collectively, we have established the function of the S. mutans CopYAZ system in copper export and have further expanded knowledge on the importance of copper homeostasis and the CopYAZ system in modulating streptococcal physiology, including stress tolerance, membrane potential, genetic competence, and biofilm formation. IMPORTANCE S. mutans is best known for its role in the initiation and progression of human dental caries, one of the most common chronic diseases worldwide. S. mutans is also implicated in bacterial endocarditis, a life-threatening inflammation of the heart valve. The core virulence factors of S. mutans include its ability to produce and sustain acidic conditions and to form a polysaccharide-encased biofilm that provides protection against environmental insults. Here, we demonstrate that the addition of copper and/or deletion of copYAZ (the copper homeostasis system) have serious implications in modulating biofilm formation, stress tolerance, and genetic transformation in S. mutans. Manipulating the pathways affected by copper and the copYAZ system may help to develop potential therapeutics to prev...

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Occurrence of Copper Proteins through the Three Domains of Life: A Bioinformatic Approach

Cited by 184 publications

References 58 publications

History of biological metal utilization inferred through phylogenomic analysis of protein structures

History of biological metal utilization inferred through phylogenomic analysis of protein structures

Copper Stress Affects Iron Homeostasis by Destabilizing Iron-Sulfur Cluster Formation in Bacillus subtilis

The copYAZ Operon Functions in Copper Efflux, Biofilm Formation, Genetic Transformation, and Stress Tolerance in Streptococcus mutans

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