title: Dps proteins prevent Fenton-mediated oxidative damage by trapping hydroxyl radicals within the protein shell.
abstract: Dps (DNA-binding proteins from starved cells) proteins belong to a widespread bacterial family of proteins expressed under nutritional and oxidative stress conditions. In particular, Dps proteins protect DNA against Fenton-mediated oxidative stress, as they catalyze iron oxidation by hydrogen peroxide at highly conserved ferroxidase centers and thus reduce significantly hydroxyl radical production. This work investigates the possible generation of intraprotein radicals during the ferroxidation reaction by Escherichia coli and Listeria innocua Dps, two representative members of the family. Stopped-flow analyses show that the conserved tryptophan and tyrosine residues located near the metal binding/oxidation center are in a radical form after iron oxidation by hydrogen peroxide. DNA protection assays indicate that the presence of both residues is necessary to limit release of hydroxyl radicals in solution and the consequent oxidative damage to DNA. In general terms, the demonstration that conserved protein residues act as a trap that dissipates free electrons generated during the oxidative process brings out a novel role for the Dps protein cage.
authors.affiliation: CNR Institute of Molecular Biology and Pathology, Department of Biochemical Sciences A. Rossi-Fanelli, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bellapadrona
authors.forename: Matteo
authors.initials: M
authors.lastname: Ardini
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Ceci
authors.forename: Simonetta
authors.initials: S
authors.lastname: Stefanini
authors.forename: Emilia
authors.initials: E
authors.lastname: Chiancone
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D002570:Ceruloplasmin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008087:Listeria / Q000235:genetics* / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D011485:Protein Binding
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C083911:DPS protein, Bacteria; C045076:Fenton's reagent; D016166:Free Radical Scavengers; D050505:Mutant Proteins; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; D002570:Ceruloplasmin