Crystal structure of Streptococcus suis Dps-like peroxide resistance protein Dpr: implications for iron incorporation

The Dps-like peroxide resistance protein (Dpr) is an aerotolerance and hydrogen peroxide resistance agent found in the meningitis-associated pathogen Streptococcus suis. Dpr is believed to act by binding free intracellular iron to prevent Fenton chemistry-catalysed formation of toxic hydroxyl radicals. The crystal structure of Dpr has been determined to 1.95 A resolution. The final model has an Rcyst value of 18.5% (Rfree = 22.4%) and consists of 12 identical monomers (each of them comprising a four alpha-helix bundle) that form a hollow sphere obeying 23 symmetry. Structural features show that Dpr belongs to the Dps family of bacterial proteins. Twelve putative ferroxidase centers, each formed at the interface of neighboring monomer pairs, were identified in the Dpr structure with structural similarities to those found in other Dps family members. Dpr was crystallized in the absence of iron, hence no bound iron was found in the structure in contrast to other Dps family members. A novel metal-binding site approximately 6A from the ferroxidase centre was identified and assigned to a bound calcium ion. Two residues from the ferroxidase centre (Asp63 and Asp74) were found to be involved in calcium binding. Structural comparison with other family members revealed that Asp63 and Asp74 adopt different conformation in the Dpr structure. The structure of Dpr presented here shows potential local conformational changes that may occur during iron incorporation. A role for the metal-binding site in iron uptake is proposed.