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DNA-binding proteins from starved cells (Dps) are
bacterial Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...
proteins that belong to the
ferritin Ferritin is a universal intracellular and extracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. ...
superfamily and are characterized by strong similarities but also distinctive differences with respect to "canonical"
ferritin Ferritin is a universal intracellular and extracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. ...
s. Dps proteins are part of a complex bacterial defence system that protects
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
against
oxidative damage Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...
and are distributed widely in the bacterial kingdom.


Description

Dps are highly symmetrical dodecameric proteins of 20 kDa characterized from a shell-like structure of 2:3 tetrahedral symmetry assembled from identical subunits with an external diameter of ~ 9 nm and a central cavity of ~ 4.5 nm in diameter. Dps proteins belong to the
ferritin Ferritin is a universal intracellular and extracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. ...
superfamily and the
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
protection is afforded by means of a double mechanism: The first was discovered in ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' Dps in 1992 and has given the name to the
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
family; during stationary phase, Dps binds the
chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
non-specifically, forming a highly ordered and stable Dps-
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
co-crystal within which chromosomal
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
is condensed and protected from diverse damages. The lysine-rich N-terminus is required for self-aggregation as well as for Dps-driven
DNA condensation DNA condensation refers to the process of compacting DNA molecules ''in vitro'' or ''in vivo''. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems. Condensed DNA often has surpr ...
. The second mode of protection is due to the ability of Dps proteins to bind and oxidize Fe(II) at the characteristic, highly conserved intersubunit
ferroxidase Ferroxidase also known as Fe(II):oxygen oxidoreductase is an enzyme that catalyzes the oxidization of iron II to iron III: : 4 Fe2+ + 4 H+ + O2 ⇔ 4 Fe3+ + 2H2O Examples Human genes encoding proteins with ferroxidase activity include: * C ...
center. The dinuclear ferroxidase centers are located at the interfaces between subunits related by 2-fold symmetry axes. Fe(II) is sequestered and stored in the form of Fe(III) oxyhydroxide mineral, which can be released after reduction. In the mineral iron core up to 500 Fe(III) can be deposited. One hydrogen peroxide oxidizes two Fe2+ ions, which prevents hydroxyl radical production by the
Fenton reaction Fenton's reagent is a solution of hydrogen peroxide (H2O2) and an iron catalyst (typically iron(II) sulfate, FeSO4). It is used to oxidize contaminants or waste water as part of an advanced oxidation process. Fenton's reagent can be used to destr ...
(reaction I): 2 Fe2+ + H2O2 + 2 H+ = 2 Fe3+ + 2 H2O Dps also protects the cell from UV and
gamma ray A gamma ray, also known as gamma radiation (symbol ), is a penetrating form of electromagnetic radiation arising from high energy interactions like the radioactive decay of atomic nuclei or astronomical events like solar flares. It consists o ...
irradiation, iron and copper toxicity, thermal stress and acid and base shocks. Also shows a weak catalase activity.


DNA condensation

Dps dodecamers can condense DNA ''in vitro'' through a
cooperative binding Cooperative binding occurs in molecular binding systems containing more than one type, or species, of molecule and in which one of the partners is not mono-valent and can bind more than one molecule of the other species. In general, molecular bindi ...
mechanism. Deletion of portions of the N-terminus or mutation of key lysine residues in the N-terminus can impair or eliminate the condensation activity of Dps. Single molecule studies have shown that Dps-DNA complexes can get trapped in long-lived metastable states that exhibit hysteresis. Because of this, the extent of DNA condensation by Dps can depend not only on the current buffer conditions but also on the conditions in the past. A modified
Ising model The Ising model (or Lenz–Ising model), named after the physicists Ernst Ising and Wilhelm Lenz, is a mathematical models in physics, mathematical model of ferromagnetism in statistical mechanics. The model consists of discrete variables that r ...
can be used to explain this binding behavior. The nucleation of Dps condensation on DNA requires multiple DNA strands close proximity (similar size as Dps). For instance, Dps shows higher preference towards supercoiled DNA where two DNA strands are in closer vicinity.


Expression

In ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' Dps protein is Induced by rpoS and IHF in the early stationary phase. Dps is also Induced by oxyR in response to oxidative stress during exponential phase. ClpXP probably directly regulate proteolysis of dps during exponential phase. ClpAP seems to play an indirect role in maintaining ongoing dps synthesis during stationary phase


Applications


For nanoparticle synthesis

Cavities formed by Dps and
ferritin Ferritin is a universal intracellular and extracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. ...
proteins have been successfully used as the reaction chamber for the fabrication of metal
nanoparticles A nanoparticle or ultrafine particle is a particle of matter 1 to 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 100 nm in only two directions. At ...
(NPs). Protein shells served as a template to restrain particle growth and as a coating to prevent coagulation/aggregation between NPs. Using various sizes of protein shells, various sizes of NPs can be easily synthesized for chemical, physical and bio-medical applications.


For enzyme encapsulation

Nature utilizes protein-based architectures to house enzymes within its interior cavity, for example: encapsulin and carboxysomes. Taking inspiration from nature, hollow interior cavity of Dps and ferritin cages have also been used to encapsulate enzymes. Cytochrome C, a hemoprotein with peroxidase-like activity when encapsulated inside Dps cage showed better catalytic activity over broad pH range compared to free enzyme in bulk solution. This behavior was attributed to high local concentration of enzyme inside Dps and unique microenvironment provided by Dps interior cavity.


For targeted drug delivery

Delivery of cargo at intended target site remains major concern for targeted drug delivery owing to presence of biological barriers and enhanced permeability and retention (EPR) effects. Furthermore, formation of protein corona around injected nanoparticles is also a topic of interest within the targeted delivery field. Researchers tried to overcome these concerns by using natural bio-distribution of protein cage nanoparticles for cargo delivery. For example, DNA binding protein from nutrient starved cells (Dps) cage was shown to cross glomerular filtration barrier and target renal proximal tubules.


See also

*
Bacterioferritin Bacterioferritin (Bfr) is an oligomeric protein containing both a binuclear iron centre and haem b. The Tertiary (chemistry), tertiary and quaternary structure of Bfr is very similar to that of ferritin. The physiological functions of BFR, which ma ...
*
Transferrin Transferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Iron(III), Fe3+ ions. Human transferrin is ...
*
Ferritin Ferritin is a universal intracellular and extracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. ...


References

{{DEFAULTSORT:Dps (Dna-Binding Proteins From Starved Cells) Iron metabolism DNA-binding proteins