The Multi-layered Structure of Dps with a Novel Di-nuclear Ferroxidase Center

Ren, Bin; Tibbelin, Gudrun; Kajino, Toshitaka; Asami, Osamu; Ladenstein, Rudolf

doi:10.1016/s0022-2836(03)00466-2

Cited by 110 publications

(128 citation statements)

References 26 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…Although the DNA-binding domain in Dps proteins are not well defined, basic residues in either the N-terminal or C-terminal regions have been implicated. For example, extension of the N-terminal E. coli Dps subunit or in the C-terminal extension of the Mycobacterium smegmatis Dps subunit have been implicated in DNA binding (33,36,37). These suggestions have recently been corroborated by N-terminal deletion mutants of E. coli Dps that do not bind DNA (38).…”

Section: Resultsmentioning

confidence: 97%

See 1 more Smart Citation

An archaeal antioxidant: Characterization of a Dps-like protein from Sulfolobus solfataricus

Wiedenheft

Mosolf

Willits

et al. 2005

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

107

110

View full text Add to dashboard Cite

Evolution of an oxygenic atmosphere required primordial life to accommodate the toxicity associated with reactive oxygen species. We have characterized an archaeal antioxidant from the hyperthermophilic acidophile Sulfolobus solfataricus. The amino acid sequence of this Ϸ22-kDa protein shares little sequence similarity with proteins with known function. However, the protein shares high sequence similarity with hypothetical proteins in other archaeal and bacterial genomes. Nine of these hypothetical proteins form a monophyletic cluster within the broad superfamily of ferritin-like diiron-carboxylate proteins. Higher order structural predictions and image reconstructions indicate that the S. solfataricus protein is structurally related to a class of DNA-binding protein from starved cells (Dps). The recombinant protein self assembles into a hollow dodecameric protein cage having tetrahedral symmetry (SsDps). The outer shell diameter is Ϸ10 nm, and the interior diameter is Ϸ5 nm. Dps proteins have been shown to protect nucleic acids by physically shielding DNA against oxidative damage and by consuming constituents involved in Fenton chemistry. In vitro, the assembled archaeal protein efficiently uses H2O2 to oxidize Fe(II) to Fe(III) and stores the oxide as a mineral core on the interior surface of the protein cage. The ssdps gene is upregulated in S. solfataricus cultures grown in iron-depleted media and upon H2O2 stress, but is not induced by other stresses. SsDps-mediated reduction of hydrogen peroxide and possible DNA-binding capabilities of this archaeal Dps protein are mechanisms by which S. solfataricus mitigates oxidative damage.ferritin ͉ iron ͉ oxidative stress ͉ biomineralization ͉ hyperthermophile

show abstract

Section: Resultsmentioning

confidence: 97%

“…In all previously characterized Dps proteins, this redox reaction is mediated by a unique diiron-binding motif (Fig. 11) (16,33,36,37,41). This motif has been implicated in coordinating the two-electron reduction of H 2 O 2.…”

Section: Discussionmentioning

confidence: 99%

An archaeal antioxidant: Characterization of a Dps-like protein from Sulfolobus solfataricus

Wiedenheft

Mosolf

Willits

et al. 2005

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

107

110

View full text Add to dashboard Cite

show abstract

“…In the Listeria ferritin and Dps from E. coli, a hydrophilic pore with a diameter of Ϸ8 Å runs between the ␣4␣5 loops of three symmetry-related subunits and is exclusively formed by acidic residues. Because these features are well conserved among 12-and 24-mer ferritins, it was suggested that the pore region around this threefold axis represents the major entrance site for Fe 2ϩ into the ferritin protein shell (4,13,26). In the halophilic ferritin dodecamer, this pore is plugged by a row of four residues, Glu-141, His-150, Arg-153, and Glu-154 (not shown).…”

Section: Structural Comparison Of Dpsa With 24-mer Ferritins and Dps-mentioning

confidence: 99%

Iron-oxo clusters biomineralizing on protein surfaces: Structural analysis of Halobacterium salinarum DpsA in its low- and high-iron states

Zeth

Offermann

Essen

et al. 2004

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

107

122

View full text Add to dashboard Cite

The crystal structure of the Dps-like (Dps, DNA-protecting protein during starvation) ferritin protein DpsA from the halophile Halobacterium salinarum was determined with low endogenous iron content at 1.6-Å resolution. The mechanism of iron uptake and storage was analyzed in this noncanonical ferritin by three highresolution structures at successively increasing iron contents. In the high-iron state of the DpsA protein, up to 110 iron atoms were localized in the dodecameric protein complex. For ultimate iron storage, the archaeal ferritin shell comprises iron-binding sites for iron translocation, oxidation, and nucleation. Initial iron-protein interactions occur through acidic residues exposed along the outer surface in proximity to the iron entry pore. This narrow pore permits translocation of ions toward the ferroxidase centers via two discrete steps. Iron oxidation proceeds by transient formation of tri-iron ferroxidase centers. Iron storage by biomineralization inside the ferritin shell occurs at two iron nucleation centers. Here, a single iron atom provides a structural seed for iron-oxide cluster formation. The clusters with up to five iron atoms adopt a geometry that is different from natural biominerals like magnetite but resembles iron clusters so far known only from bioinorganic model compounds.ferritin ͉ iron-binding ͉ inorganic cluster formation ͉ x-ray crystal structure

show abstract

“…The relatively low resolution of our crystal does not allow a detailed description of this site. The electron density map is clear enough to allow us to state that two ions are present in each site, as in the case of B. brevis Dps structure [21]. Two Fe ions were refined in each site, along with two water molecules.…”

Section: The Ferroxidase Centermentioning

confidence: 99%

“…Three-dimensional model of the NapA monomer and oligomer. (A) Superposition of Cα chain trace of monomer of NapA (yellow) to that of other proteins of the family: Dps from Bacillus brevis (blue, PDB code 1N1Q) [21], HP-NAP from Helicobacter pylori (green, PDB code 1JI4) [18], Dlp-2 from Bacillus anthracis (red, PDB code 1JIG) [17]. Residues are numbered according to [7].…”

Section: N-and C-terminal Tails Of Napa Are Not Crucial For Its Pro-tmentioning

confidence: 99%

Structure and immunomodulatory property relationship in NapA of Borrelia burgdorferi

Codolo

Papinutto

Polenghi

et al. 2010

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

View full text Add to dashboard Cite

NapA from Borrelia burgdorferi is a member of the Dps-like protein family with specific immunomodulatory properties; in particular, NapA is able to induce the expression of IL-23 in neutrophils and monocytes, as well as the expression of IL-6, IL-1β, and transforming growth factor beta (TGF-β) in monocytes, via Toll-like receptor (TLR) 2. Such an activity on innate immune cells triggers a synovial fluid Th17 response. Here we report the crystal structure of NapA, determined at 2.6 Å resolution, which shows that the quaternary structure of the protein is that of a dodecamer with 23 symmetry, typical of the proteins of the family. We also demonstrate that the N-and C-terminal tails, which are flexible and not visible in the crystal, are not relevant for its pro-Th17 activity. Based on the crystal structure and on the comparison with the structure of the orthologous protein from Helicobacter pylori, HP-NAP, we hypothesize that the charge distributions on the two proteins' surfaces are responsible for the interaction with TLR2 and for the different behaviors in modulating the immune response.

show abstract

The Multi-layered Structure of Dps with a Novel Di-nuclear Ferroxidase Center

Cited by 110 publications

References 26 publications

An archaeal antioxidant: Characterization of a Dps-like protein from Sulfolobus solfataricus

An archaeal antioxidant: Characterization of a Dps-like protein from Sulfolobus solfataricus

Iron-oxo clusters biomineralizing on protein surfaces: Structural analysis of Halobacterium salinarum DpsA in its low- and high-iron states

Structure and immunomodulatory property relationship in NapA of Borrelia burgdorferi

Contact Info

Product

Resources

About