Kineococcus radiotolerans Dps forms a heteronuclear Mn–Fe ferroxidase center that may explain the Mn-dependent protection against oxidative stress

Ardini, Matteo; Fiorillo, Annarita; Fittipaldi, Maria; Stefanini, Simonetta; Gatteschi, Dante; Ilari, Andrea; Chiancone, Emilia

doi:10.1016/j.bbagen.2013.02.003

Cited by 26 publications

(25 citation statements)

References 40 publications

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“…Another example of this type of cofactor replacement is the iron sequestration protein, Dps, in Kineococcus radiotolerans (Figure 2). Dps is a binuclear Fe-containing ferroxidase that binds Fe and precipitates iron oxide inside of the Dps dodecamer; however, the K. radiotolerans enzyme is also active as a mixed metal Mn-Fe enzyme, further evidence for the protective role of Mn(II) via cofactor substitution in the oxidative stress response (Ardini et al, 2013). …”

Section: Manganese As An Antioxidant Micronutrientmentioning

confidence: 99%

Manganese acquisition and homeostasis at the host-pathogen interface

Lisher

Giedroc

2013

Front. Cell. Infect. Microbiol.

116

127

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Pathogenic bacteria acquire transition metals for cell viability and persistence of infection in competition with host nutritional defenses. The human host employs a variety of mechanisms to stress the invading pathogen with both cytotoxic metal ions and oxidative and nitrosative insults while withholding essential transition metals from the bacterium. For example, the S100 family protein calprotectin (CP) found in neutrophils is a calcium-activated chelator of extracellular Mn and Zn and is found in tissue abscesses at sites of infection by Staphylococcus aureus. In an adaptive response, bacteria have evolved systems to acquire the metals in the face of this competition while effluxing excess or toxic metals to maintain a bioavailability of transition metals that is consistent with a particular inorganic “fingerprint” under the prevailing conditions. This review highlights recent biological, chemical and structural studies focused on manganese (Mn) acquisition and homeostasis and connects this process to oxidative stress resistance and iron (Fe) availability that operates at the human host-pathogen interface.

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Section: Manganese As An Antioxidant Micronutrientmentioning

confidence: 99%

Manganese acquisition and homeostasis at the host-pathogen interface

Lisher

Giedroc

2013

Front. Cell. Infect. Microbiol.

116

127

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“…SOD activity in S. aureus is significantly diminished in the presence of the host Mn chelator CP and following deletion of the S. aureus Mn importers, mntABC and mntH , supporting the idea that Mn is the Mn‐SOD cofactor in vivo (Kehl‐Fie et al ., , ). Mn is also important for the function of Dps, a protein that protects against hydrogen peroxide via DNA binding, Fe sequestration, and ferroxidase‐activity that reduces H 2 O 2 to H 2 O (Almiron et al ., ; Martinez and Kolter, ; Su et al ., ; Anjem and Imlay, ; Zhao et al ., ; Ardini et al ., ). Mn binds to a regulatory site within Dps to permit DNA‐binding activity and inhibit ferroxidase activity, which serves as a regulatory mechanism that physically separates the two activities such that hydroxide radicals are not produced directly adjacent to DNA (Nguyen and Grove, ).…”

Section: Bacterial Processes That Require Mn During Infectionmentioning

confidence: 97%

“…A distinct, high‐affinity Mn‐binding site is required for ferroxidase activity (Ardini et al ., ); thus, Mn is essential for the full repertoire of Dps function. In addition to its contributions as an enzymatic cofactor, Mn also functions as an antioxidant in a protein‐independent mechanism (Archibald and Fridovich, ; Chang and Kosman, ; Inaoka et al ., ; Tseng et al ., ; Seib et al ., ; Daly et al ., ; Barnese et al ., ; Ardini et al ., ; Culotta and Daly, ; Sharma et al ., ; Tabares and Un, ). This topic has been thoroughly reviewed (Aguirre and Culotta, ; Lisher and Giedroc, ).…”

Section: Bacterial Processes That Require Mn During Infectionmentioning

confidence: 99%

Manganese homeostasis and utilization in pathogenic bacteria

Juttukonda

Skaar

2015

Molecular Microbiology

107

129

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Summary Manganese is a required cofactor for all forms of life. Given the importance of Mn to bacteria, the host has devised strategies to sequester Mn from invaders. In the macrophage phagosome, NRAMP1 removes Mn and other essential metals to starve intracellular pathogens; in the extracellular space, calprotectin chelates Mn and Zn. Calprotectin-mediated Mn sequestration is a newly appreciated host defense mechanism and recent findings are highlighted herein. In order to acquire Mn when extracellular concentrations are low, bacteria have evolved efficient Mn acquisition systems that are under elegant transcriptional control. To counteract Mn overload, some bacteria possess Mn-specific export systems which are important in vivo, presumably for control of intracellular Mn levels. Mn transporters, their transcriptional regulators, and some Mn-requiring enzymes are necessary for virulence of certain bacterial pathogens, as revealed by animal models of infection. Furthermore, Mn is an important facet of the cellular response to oxidative stress, a host antibacterial strategy. The battle for Mn between host and pathogen is now appreciated to be a major determinant of the outcome of infection. In this MicroReview, the contribution of Mn to the host-pathogen interaction is reviewed and key questions are proposed for future study.

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“…It has been previously reported that Mn 2+ can bind to the FOC of Dps (Ardini et al, 2013), which is expected as Fe 2+ and Mn 2+ can assume similar coordination geometries in protein crystal structures (Haikarainen et al, 2011;Zheng et al, 2008). We evaluated the binding of manganese to CjDps by measuring the intrinsic tryptophan fluorescence (Fig.…”

Section: Metal-binding Analysismentioning

confidence: 99%

“…The Streptococcus suis Dps can bind Cu 2+ , Ni 2+ , Co 2+ and Mn 2+ to the FOC, as determined by isothermal titration calorimetry and X-ray crystallography (Haikarainen et al, 2011). Furthermore, Kineococcus radiotolerans Dps can form an Mn-Fe heteronuclear metal cluster at the FOC; however, only iron can be stored inside the protein shell (Ardini et al, 2013). Conserved residues are shaded in black and the arrows indicate the conserved residues at the Dps FOC.…”

Section: Introductionmentioning

confidence: 99%

Conserved histidine residues at the ferroxidase centre of the Campylobacter jejuni Dps protein are not strictly required for metal binding and oxidation

Sanchuki¹,

Valdameri²,

Moure³

et al. 2016

Microbiology

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Iron is an essential micronutrient for living organisms as it is involved in a broad variety of important biological processes. However, free iron inside the cell could be potentially toxic, generating hydroxyl radicals through the Fenton reaction. Dps (DNA-binding protein from starved cells) belongs to a subfamily of ferritins and can store iron atoms inside the dodecamer. The presence of a ferroxidase centre, composed of highly conserved residues, is a signature of this protein family. In this study, we analysed the role of two conserved histidine residues (H25 and H37) located at the ferroxidase centre of the Campylobacter jejuni Dps protein by replacing them with glycine residues. The C. jejuni H25G/H37G substituted variant showed reduced iron binding and ferroxidase activities in comparison with wt Dps, while DNA-binding activity remained unaffected. We also found that both CjDps wt and CjDps H25G/H37G were able to bind manganese atoms. These results indicate that the H25 and H37 residues at the ferroxidase centre of C. jejuni Dps are not strictly required for metal binding and oxidation.

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Kineococcus radiotolerans Dps forms a heteronuclear Mn–Fe ferroxidase center that may explain the Mn-dependent protection against oxidative stress

Abstract: The results provide a likely molecular mechanism for the protective role of Mn(II) under oxidative stress conditions as it participates in redox cycling in the hetero-binuclear ferroxidase center.

Cited by 26 publications

References 40 publications

Manganese acquisition and homeostasis at the host-pathogen interface

Manganese acquisition and homeostasis at the host-pathogen interface

Manganese homeostasis and utilization in pathogenic bacteria

Conserved histidine residues at the ferroxidase centre of the Campylobacter jejuni Dps protein are not strictly required for metal binding and oxidation

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