The crystal structure of Dps, a ferritin homolog that binds and protects DNA

Grant, Robert A.; Filman, David J.; Finkel, Steven E.; Kolter, Roberto; Hogle, James M.

doi:10.1038/nsb0498-294

Cited by 500 publications

(603 citation statements)

References 35 publications

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“…14,18,21 It should be noted that the aromatic residue W52 was identified at both the twofold and the Dps-like threefold interface by Protein Interfaces, Surfaces and Assemblies (PISA) 22 analysis, however, the energetic effect was predicted to be more significant at the twofold interface (data not shown). The acidic residue D78 appears to be interacting with both K48 and R70 [ Fig.…”

Section: Selection Of Interfacial Residues For Mutagenesismentioning

confidence: 98%

“…Through simple inspection of the E. coli DPS crystal structure (PDB ID: 1dps) eight such residues were identified. 14 Thus, Y16, R18, W52, D78, R83, R133, D146, and W160 were selected for mutagenesis (Fig. 2).…”

Section: Selection Of Interfacial Residues For Mutagenesismentioning

confidence: 99%

“…[14][15][16][17] The homo-oligomerization and tractable self-assembly mechanism of ferritins make them an ideal system to understand the vital role protein-protein interactions play in protein folding and in higher order quaternary structure.…”

Section: Introductionmentioning

confidence: 99%

“…14 We have recently performed alanine shaving of the proteinprotein interfaces in the maxi-ferritin BFR from Escherichia coli to identify residues that control its stability and oligomerization. 18,19 As an extension of this latter work, we describe here the application of this strategy to E. coli DPS (EcDPS).…”

Section: Introductionmentioning

confidence: 99%

“…In the Dps family, the ferrioxidase center is located at the twofold symmetry axis between two monomers rather than being embedded in the four-helix bundle of a single subunit in BFR. 14,20 So, although the monomer structures are similar, clearly, the underlying fundamentals that control the oligomer architecture and how these relate to the activity of these two subfamilies of protein cages are significantly different. Establishing the similarities and divergences in these proteins' structural energetics is an initial step in our long-term goal of converting, with a minimum of mutations, a mini-ferritin monomer into one that assembles into a maxi-ferritin and vice versa.…”

Section: Introductionmentioning

confidence: 99%

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Rational disruption of the oligomerization of the mini‐ferritin E. coli DPS through protein‐protein interface mutation

Zhang

Chee

et al. 2011

Protein Science

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DNA-binding protein from starved cells (DPS), a mini-ferritin capable of self-assembling into a 12-meric nano-cage, was chosen as the basis for an alanine-shaving mutagenesis study to investigate the importance of key amino acid residues, located at symmetry-related protein-protein interfaces, in controlling protein stability and self-assembly. Nine mutants were designed through simple inspection, synthesized, and subjected to transmission electron microscopy, circular dichroism, size exclusion chromatography, and ''virtual alanine scanning'' computational analysis. The data indicate that many of these residues may be hot spot residues. Most remarkably, two residues, R83 and R133, were observed to shift the oligomerization state to~50% dimer. Based on the hypothesis that these two residues constitute a ''hot strip,'' located at the ferritin-like threefold axis, the double mutant was generated which completely shuts down detectable formation of 12-mer in solution, favoring a cooperatively folded dimer. The fact that this effect logically builds upon the single mutants emphasizes that complex self-assembly has the potential to be manipulated rationally. This study should have an impact on the fundamental understanding of the assembly of DPS protein cages specifically and protein quaternary structure in general. In addition, as there is much interest in applying these and similar systems to the templation of nano-materials and drug delivery, the ability to control this ferritin's oligomerization state and stability could prove especially valuable.

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Section: Selection Of Interfacial Residues For Mutagenesismentioning

confidence: 98%

Section: Selection Of Interfacial Residues For Mutagenesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Rational disruption of the oligomerization of the mini‐ferritin E. coli DPS through protein‐protein interface mutation

Zhang

Chee

et al. 2011

Protein Science

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DNA ‐Binding Proteins From Starved Cells ( Dps Proteins)

Stefanini

Ceci

Ardini

et al. 2004

Handbook of Metalloproteins

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In the recent past over 200 Dps (DNA‐binding proteins from starved cells) proteins have been identified in bacterial genomes. Dps proteins belong to the ferritin superfamily. They are expressed under conditions of oxidative and/or nutritional stress and are characterized by a highly conserved shell‐like structure of 12 identical subunits assembled with 23 symmetry. The internal cavity is designed to accommodate up to 500 iron/atoms per molecule in a soluble and bioavailable form. Dps proteins play an important role in the complex protection mechanism against oxidative damage. The presence of a highly conserved ferroxidase center, which uses hydrogen peroxide as physiological iron oxidant, confers to all Dps proteins the capacity to decrease the production of the hydroxyl‐radicals and, hence, to prevent the damage to DNA and other cellular components. Ferroxidase activity is of special importance in pathogenic bacteria since production of hydrogen peroxide in macrophages and neutrophiles represents one of the first host defense mechanisms. The capacity to bind DNA in a nonspecific manner and pack it into condensed structures, an attribute limited to some members of the family, represents the second distinctive mechanism used to advantage by Dps proteins for the survival of the organism.

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Iron Proteins for Storage & Transport & Their Synthetic Analogs

Lewin

Brun

Moore

2005

Encyclopedia of Inorganic Chemistry

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This article reviews proteins involved in iron metabolism. Brief descriptions are given of the biological contexts for the proteins discussed but the main emphasis is on chemical and structural aspects of them. Iron is essential to almost all forms of life, but its low bioavailability and toxicity mean that they require sophisticated mechanisms to transport it. Mammals acquire heme and nonheme iron via proteins in the gut wall, and transport it around the body using serum transferrin, for ferric iron, and hemopexin, for heme. Microbes have an active iron uptake mechanism involving small iron chelators called siderophores, for example, ferrichrome in Escherichia coli . Ferrichrome enters the cell via FhuA, a β‐barrel in the outer membrane. The periplasmic protein FhuD then transfers it to the FhuBC complex in the cytoplasmic membrane. FhuB forms a channel through which the ferric siderophore passes using energy supplied by FhuC. Once inside the cytoplasm the iron is removed from the ligand, possibly via reduction by FhuF. Some pathogenic bacteria have a similar system for heme uptake, secreting hemophores such as HasA, which can remove heme from hemoglobin. Other pathogens have outer membrane receptors that remove ferric iron from transferrin and transport it into the periplasm, where it is bound by ferric binding proteins that closely resemble a single lobe of transferrin. Following its acquisition, iron needs to be stored safely. The most widespread form of iron storage is the ferritin superfamily, which includes ferritin, bacterioferritin, and Dps. Ferritin is found in bacteria, plants, and animals and is a large shell made up of 24 subunits within which up to 4,500 ferric ions can be stored as a ferrihydrite mineral core. Bacterioferritin is found in bacteria and is closely related to ferritin, but contains up to 12 heme groups bound between pairs of subunits, which may play a role in iron release or electron storage. The bacterial protein Dps is smaller than ferritin, with 12 subunits forming the protein shell, and can hold up to 500 ferric ions. All of these proteins contain dinuclear iron sites that catalyze the oxidation of ferrous iron. An alternative form of iron storage is frataxin, found in mitochondria. Although not related to ferritin, this protein has the ability to form large aggregates that can store up to 50 ferric ions per monomer in a mineral core resembling those of ferritins.

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The crystal structure of Dps, a ferritin homolog that binds and protects DNA

Cited by 500 publications

References 35 publications

Rational disruption of the oligomerization of the mini‐ferritin E. coli DPS through protein‐protein interface mutation

Rational disruption of the oligomerization of the mini‐ferritin E. coli DPS through protein‐protein interface mutation

DNA ‐Binding Proteins From Starved Cells ( Dps Proteins)

Iron Proteins for Storage & Transport & Their Synthetic Analogs

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