A Histidine Aspartate Ionic Lock Gates the Iron Passage in Miniferritins from Mycobacterium smegmatis

Williams, Sunanda Margrett; Chandran, Anu V.; Vijayabaskar, M.; Roy, Sourav; Balaram, Hemalatha; Vishveshwara, Saraswathi; Vijayan, M.; Chatterji, Dipankar

doi:10.1074/jbc.m113.524421

Cited by 17 publications

(10 citation statements)

References 67 publications

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“…The authors suggested that the His, which are not conserved among Dps, could influence the conformations of the Asp thereby favoring iron uptake or its release out of the Dps. [52]. Also for the HsDpsA a similar amino acid arrangement (cavity, Glu154, Arg153, His150, Glu141, towards exterior) was found, although in a closed state, in which the translocation of Fe 2+ was unlikely [31].…”

Section: Discussionmentioning

confidence: 97%

“…Similar to the cap-like structure in NpDps4, C-terminal extensions were found in the Deinococcus radiodurans Dps1 (DrDps1), although blocking the entry of the pore [53]. But more often the blockade is caused by bulky side chains within the channel impeding a possible metal ion translocation [5,16,52,54–56]. The interface at the Dps-like pore has additionally been identified to be a crucial structural element that evolutionarily links maxiferritins with Dps proteins [57].…”

Section: Discussionmentioning

confidence: 99%

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The Dps4 from Nostoc punctiforme ATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

Howe

Moparthi

et al. 2019

PLoS ONE

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Dps proteins (DNA-binding proteins from starved cells) have been found to detoxify H 2 O 2 . At their catalytic centers, the ferroxidase center (FOC), Dps proteins utilize Fe 2+ to reduce H 2 O 2 and therefore play an essential role in the protection against oxidative stress and maintaining iron homeostasis. Whereas most bacteria accommodate one or two Dps, there are five different Dps proteins in Nostoc punctiforme , a phototrophic and filamentous cyanobacterium. This uncommonly high number of Dps proteins implies a sophisticated machinery for maintaining complex iron homeostasis and for protection against oxidative stress. Functional analyses and structural information on cyanobacterial Dps proteins are rare, but essential for understanding the function of each of the NpDps proteins. In this study, we present the crystal structure of NpDps4 in its metal-free, iron- and zinc-bound forms. The FOC coordinates either two iron atoms or one zinc atom. Spectroscopic analyses revealed that NpDps4 could oxidize Fe 2+ utilizing O 2 , but no evidence for its use of the oxidant H 2 O 2 could be found. We identified Zn 2+ to be an effective inhibitor of the O 2 -mediated Fe 2+ oxidation in NpDps4. NpDps4 exhibits a FOC that is very different from canonical Dps, but structurally similar to the atypical one from DpsA of Thermosynechococcus elongatus . Sequence comparisons among Dps protein homologs to NpDps4 within the cyanobacterial phylum led us to classify a novel FOC class: the His-type FOC. The features of this special FOC have not been identified in Dps proteins from other bacterial phyla and it might be unique to cyanobacterial Dps proteins.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

The Dps4 from Nostoc punctiforme ATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

Howe

Moparthi

et al. 2019

PLoS ONE

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show abstract

“…The authors suggested that the His, which are not conserved among Dps, could influence the conformations of the Asp thereby favoring iron uptake or its release out of the Dps. [51]. Also for the HsDpsA a similar amino acid arrangement (cavity, Glu154, Arg153, His150, Glu141, towards exterior) was found, although in a closed state, in which the translocation of Fe 2+ was unlikely [31].…”

Section: Discussionmentioning

confidence: 97%

“…Similar to the cap-like structure in NpDps4, the C-terminal extension in DrDps1 was also found to block the entry [52]. But more often the blockade is caused by bulky side chains within the channel impeding a possible metal ion translocation [5,16,51,53–55].…”

Section: Discussionmentioning

confidence: 97%

The Dps4 fromNostoc punctiformeATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

Howe

Moparthi

et al. 2019

Preprint

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25Dps proteins (DNA-binding proteins from starved cells) have been found to detoxify H 2 O 2 . At 26 their catalytic centers, the ferroxidase center (FOC), Dps proteins utilize Fe 2+ to reduce H 2 O 2 27 and therefore play an essential role in the protection against oxidative stress and maintaining 28 iron homeostasis. Whereas most bacteria accommodate one or two Dps, there are five 29 different Dps proteins in Nostoc punctiforme, a phototrophic and filamentous cyanobacterium. 30 This uncommonly high number of Dps proteins implies a sophisticated machinery for 31 maintaining complex iron homeostasis and for protection against oxidative stress. Functional 32 analyses and structural information on cyanobacterial Dps proteins are rare, but essential for 33 understanding the function of each of the NpDps proteins. In this study, we present the crystal 34 structure of NpDps4 in its metal-free, iron-and zinc-bound forms. The FOC coordinates either 35 two iron atoms or one zinc atom. Spectroscopic analyses revealed that NpDps4 could oxidize 36 Fe 2+ utilizing O 2 , but no evidence for its use of the oxidant H 2 O 2 could be found. We identified 37 Zn 2+ to be an effective inhibitor of the O 2 -mediated Fe 2+ oxidation in NpDps4. NpDps4 exhibits 38 a FOC that is very different from canonical Dps, but structurally similar to the atypical one from 39 DpsA of Thermosynechococcus elongatus. Sequence comparisons among Dps protein 40 homologs to NpDps4 within the cyanobacterial phylum led us to classify a novel FOC class: 41 the His-type FOC. The features of this special FOC have not been identified in Dps proteins 42 from other bacterial phyla and it might be unique to cyanobacterial Dps proteins.43 Keywords: ferroxidase center, iron, oxidative stress, crystal structure, reactive oxygen 44 species 45 46 3 49 bacterioferritins (bfr) and ferritins (ftn). Dps proteins exhibit a remarkable three-dimensional 50 structure consisting of twelve monomers (or six dimers), forming a spherically shaped protein 51 complex with a hollow spherical interior [2,3]. 52 On the inside, each dimeric interface creates two identical catalytic centers, called the 53 ferroxidase centers (FOC). There, the oxidation of ferrous iron (Fe 2+ ) to ferric (Fe 3+ ) takes 54 place and an iron oxide mineral core consisting of up to 500 Fe atoms can be formed [4]. 55 Canonical FOCs in Dps proteins consist of five conserved amino acids, namely two His and 56 one Asp from one monomer as well as one Glu and one Asp from the adjacent monomer at 57 the dimer interface.58To reach the catalytic center, the Fe 2+ ions have been suggested to travel through two types 59 of pores that are connecting the internal cavity with the exterior [2]. One pore type is the ferritin-60 like pore, which is named after their structural similarity to the iron entrance pores in ferritins. 61The ferritin-like pore has been frequently assigned to be the iron entrance pore due to its 62 negatively charged character in canonical Dps structures. The other pore type, the Dps-type 63 pore, i...

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“…The free Fe ion can act catalytically via the Fenton reaction to produce hydroxyl radicals that damage lipids, proteins, and DNA [ 40 ]; as a result, free intracellular Fe must be maintained at low levels [ 21 ]. The proteins of the ferritin superfamily, which include ferritin and Dps along with bacterioferritin, are defined by their ferroxidase activity and their ability to bind Fe; they are distributed across all three domains of life [ 41 , 42 ]. The ferritins can convert Fe 2+ to Fe 3+ and then store the Fe in a nonreactive mineral form, Fe 2 O 3 , inside a protein cage.…”

Section: Discussionmentioning

confidence: 99%

A ferritin-like protein with antioxidant activity in Ureaplasma urealyticum

Dai

Chen

et al. 2015

BMC Microbiol

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BackgroundUreaplasma urealyticum is a major pathogen associated with many diseases. The ability of U. urealyticum to protect itself from oxidative stress is likely to be important for its pathogenesis and survival, but its oxidative stress tolerance mechanisms remain unclear. This study investigates the antioxidant activity of a ferritin-like protein from U. urealyticum.ResultsThe uuferritin gene, which was up regulated when U. urealyticum was subjected to oxidative stress, was cloned from U. urealyticum and the corresponding recombinant protein uuferritin was purified. Uuferritin protein reduced the levels of hydroxyl radicals generated by the Fenton reaction as a consequence of its ferroxidase activity, and thus the protein protected DNA from oxidative damage. Furthermore, oxidation-sensitive Escherichia coli mutants transformed with pTrc99a-uuferritin showed significantly improved tolerance to oxidative stress compared to E. coli mutants transformed with an empty pTrc99a vector.ConclusionsThe present work shows that uuferritin protein confers resistance to oxidative stress in vitro and in E. coli. The protective role of uuferritin provides a foundation for understanding the mechanisms of oxidative stress tolerance in U. urealyticum.

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A Histidine Aspartate Ionic Lock Gates the Iron Passage in Miniferritins from Mycobacterium smegmatis

Cited by 17 publications

References 67 publications

The Dps4 from Nostoc punctiforme ATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

The Dps4 from Nostoc punctiforme ATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

The Dps4 fromNostoc punctiformeATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

A ferritin-like protein with antioxidant activity in Ureaplasma urealyticum

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