DNA-binding protein from starved cells

DNA-binding proteins from starved cells (DPS) are bacterial proteins that belong to the ferritin superfamily and are characterized by strong similarities but also distinctive differences with respect to "canonical" ferritins.

Dps (DNA-binding proteins from starved cells)
Structure of the DPS protein (PDB: 1QGH​).[1]
Identifiers
SymbolDPS
InterProIPR002177
CDDcd01043

DPS proteins are part of a complex bacterial defence system that protects DNA against oxidative damage 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.[2][3][4] Dps proteins belong to the ferritin superfamily and the DNA protection is afforded by means of a double mechanism:

The first was discovered in Escherichia coli Dps in 1992 [5] and has given the name to the protein family; during stationary phase, Dps binds the chromosome non-specifically, forming a highly ordered and stable dps-DNA co-crystal within which chromosomal DNA is condensed and protected from diverse damages.[6] The lysine-rich N-terminus is required for self-aggregation as well as for Dps-driven DNA condensation.[7]

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 center.[8][9]

The dinuclear ferroxidase centers are located at the interfaces between subunits related by 2-fold symmetry axes.[10] 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 (reaction I):

2 Fe2+ + H2O2 + 2 H+ = 2 Fe3+ + 2 H2O

Dps also protects the cell from UV and gamma ray irradiation, iron and copper toxicity, thermal stress and acid and base shocks.[1] Also shows a weak catalase activity.

DNA condensation

Dps dodecamers can condense DNA in vitro through a cooperative binding mechanism. Deletion of portions of the N-terminus[7] or mutation of key lysine residues in the N-terminus[11] 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.[12] 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 can be used to explain this binding behavior.

Expression

In Escherichia coli 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 proteins have been successfully used as the reaction chamber for the fabrication of metal nanoparticles (NPs).[13][14][15][16] 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.[17] 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.[18]

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.[19]

See also

References
  1. Ilari A, Stefanini S, Chiancone E, Tsernoglou D (January 2000). "The dodecameric ferritin from Listeria innocua contains a novel intersubunit iron-binding site". Nature Structural Biology. 7 (1): 38–43. doi:10.1038/71236. PMID 10625425. S2CID 52872968.
  2. Grant RA, Filman DJ, Finkel SE, Kolter R, Hogle JM (April 1998). "The crystal structure of Dps, a ferritin homolog that binds and protects DNA". Nature Structural Biology. 5 (4): 294–303. doi:10.1038/nsb0498-294. PMID 9546221. S2CID 26711707.
  3. Chiancone E, Ceci P (August 2010). "The multifaceted capacity of Dps proteins to combat bacterial stress conditions: Detoxification of iron and hydrogen peroxide and DNA binding". Biochimica et Biophysica Acta (BBA) - General Subjects. 1800 (8): 798–805. doi:10.1016/j.bbagen.2010.01.013. PMID 20138126.
  4. Chiancone E, Ceci P (January 2010). "Role of Dps (DNA-binding proteins from starved cells) aggregation on DNA". Frontiers in Bioscience. 15 (1): 122–31. doi:10.2741/3610. PMID 20036810.
  5. Almirón M, Link AJ, Furlong D, Kolter R (December 1992). "A novel DNA-binding protein with regulatory and protective roles in starved Escherichia coli". Genes & Development. 6 (12B): 2646–54. doi:10.1101/gad.6.12b.2646. PMID 1340475.
  6. Wolf SG, Frenkiel D, Arad T, Finkel SE, Kolter R, Minsky A (July 1999). "DNA protection by stress-induced biocrystallization". Nature. 400 (6739): 83–5. Bibcode:1999Natur.400...83W. doi:10.1038/21918. PMID 10403254. S2CID 204994265.
  7. Ceci P, Cellai S, Falvo E, Rivetti C, Rossi GL, Chiancone E (2004). "DNA condensation and self-aggregation of Escherichia coli Dps are coupled phenomena related to the properties of the N-terminus". Nucleic Acids Research. 32 (19): 5935–44. doi:10.1093/nar/gkh915. PMC 528800. PMID 15534364.
  8. Zhao G, Ceci P, Ilari A, Giangiacomo L, Laue TM, Chiancone E, Chasteen ND (August 2002). "Iron and hydrogen peroxide detoxification properties of DNA-binding protein from starved cells. A ferritin-like DNA-binding protein of Escherichia coli". The Journal of Biological Chemistry. 277 (31): 27689–96. doi:10.1074/jbc.M202094200. PMID 12016214.
  9. Ceci P, Ilari A, Falvo E, Chiancone E (May 2003). "The Dps protein of Agrobacterium tumefaciens does not bind to DNA but protects it toward oxidative cleavage: x-ray crystal structure, iron binding, and hydroxyl-radical scavenging properties". The Journal of Biological Chemistry. 278 (22): 20319–26. doi:10.1074/jbc.M302114200. PMID 12660233.
  10. Nair S, Finkel SE (July 2004). "Dps protects cells against multiple stresses during stationary phase". Journal of Bacteriology. 186 (13): 4192–8. doi:10.1128/JB.186.13.4192-4198.2004. PMC 421617. PMID 15205421.
  11. Karas VO, Westerlaken I, Meyer AS (October 2015). "The DNA-Binding Protein from Starved Cells (Dps) Utilizes Dual Functions To Defend Cells against Multiple Stresses". Journal of Bacteriology. 197 (19): 3206–15. doi:10.1128/JB.00475-15. PMC 4560292. PMID 26216848.
  12. Vtyurina NN, Dulin D, Docter MW, Meyer AS, Dekker NH, Abbondanzieri EA (May 2016). "Hysteresis in DNA compaction by Dps is described by an Ising model". Proceedings of the National Academy of Sciences of the United States of America. 113 (18): 4982–7. Bibcode:2016PNAS..113.4982V. doi:10.1073/pnas.1521241113. PMC 4983820. PMID 27091987.
  13. Allen M, Willits D, Mosolf J, Young M, Douglas T (2002). "Protein Cage Constrained Synthesis of Ferrimagnetic Iron Oxide Nanoparticles". Advanced Materials. 14 (21): 1562–1565. doi:10.1002/1521-4095(20021104)14:21<1562::AID-ADMA1562>3.0.CO;2-D.
  14. Allen M, Willits D, Young M, Douglas T (October 2003). "Constrained synthesis of cobalt oxide nanomaterials in the 12-subunit protein cage from Listeria innocua". Inorganic Chemistry. 42 (20): 6300–5. doi:10.1021/ic0343657. PMID 14514305.
  15. Ceci P, Chiancone E, Kasyutich O, Bellapadrona G, Castelli L, Fittipaldi M, Gatteschi D, Innocenti C, Sangregorio C (January 2010). "Synthesis of iron oxide nanoparticles in Listeria innocua Dps (DNA-binding protein from starved cells): a study with the wild-type protein and a catalytic centre mutant". Chemistry: A European Journal. 16 (2): 709–17. doi:10.1002/chem.200901138. PMID 19859920.
  16. Prastaro A, Ceci P, Chiancone E, Boffi A, Cirilli R, Colone M, Fabrizi G, Stringaro A, Cacchi S (2009). "Suzuki-Miyaura cross-coupling catalyzed by protein-stabilized palladium nanoparticles under aerobic conditions in water: application to a one-pot chemoenzymatic enantioselective synthesis of chiral biaryl alcohols". Green Chemistry. 11 (12): 1929. doi:10.1039/b915184b.
  17. Tetter S, Hilvert D (November 2017). "Enzyme Encapsulation by a Ferritin Cage". Angewandte Chemie. 56 (47): 14933–14936. doi:10.1002/anie.201708530. PMID 28902449.
  18. Waghwani HK, Douglas, T (March 2021). "Cytochrome C with peroxidase-like activity encapsulated inside the small DPS protein nanocage". Journal of Materials Chemistry B. 9: 3168–3179. doi:10.1039/d1tb00234a. PMID 33885621.
  19. Uchida M, Maier B, Waghwani HK, Selivanovitch E, Pay SL, Avera J, Yun E, Sandoval RM, Molitoris BA, Zollman A, Douglas T, Hato, T (September 2019). "The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration". Journal of Clinical Investigation. 129: 3941–3951. doi:10.1172/JCI127511. PMID 31424427.
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