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Pseudomonas aeruginosa Dps (PA0962) Functions in H2O2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity
Rajapaksha, Nimesha Soldano, Anabel Yao, Huili Donnarumma, Fabrizio Kashipathy, Maithri M. Seibold, Steve Battaile, Kevin P. Lovell, Scott Rivera, Mario
Rajapaksha, Nimesha
Soldano, Anabel
Yao, Huili
Donnarumma, Fabrizio
Kashipathy, Maithri M.
Seibold, Steve
Battaile, Kevin P.
Lovell, Scott
Rivera, Mario
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Abstract
We report the structural, biochemical, and functional characterization of the product of gene PA0962 from Pseudomonas aeruginosa PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH and above. The 12-Mer Pa Dps contains two di-iron centers at the interface of each subunit dimer, coordinated by conserved His, Glu, and Asp residues. In vitro, the di-iron centers catalyze the oxidation of Fe2+ utilizing H2O2 (not O2) as an oxidant, suggesting Pa Dps functions to aid P. aeruginosa to survive H2O2-mediated oxidative stress. In agreement, a P. aeruginosa Δdps mutant is significantly more susceptible to H2O2 than the parent strain. The Pa Dps structure harbors a novel network of Tyr residues at the interface of each subunit dimer between the two di-iron centers, which captures radicals generated during Fe2+ oxidation at the ferroxidase centers and forms di-tyrosine linkages, thus effectively trapping the radicals within the Dps shell. Surprisingly, incubating Pa Dps and DNA revealed unprecedented DNA cleaving activity that is independent of H2O2 or O2 but requires divalent cations and 12-mer Pa Dps.
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Date
2023-02-28
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Publisher
MDPI
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Keywords
Dps, Mini ferritin, Ferritin, Iron metabolism, Oxidative stress, Peroxide toxicity, Exonuclease, DNA cleaving activity
Citation
Rajapaksha, N.; Soldano, A.; Yao, H.; Donnarumma, F.; Kashipathy, M.M.; Seibold, S.; Battaile, K.P.; Lovell, S.; Rivera, M. Pseudomonas aeruginosa Dps (PA0962) Functions in H2O2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity. Int. J. Mol. Sci. 2023, 24, 4669. https://doi.org/10.3390/ijms24054669