title: Dps/Dpr ferritin-like protein: insights into the mechanism of iron incorporation and evidence for a central role in cellular iron homeostasis in Streptococcus suis.
abstract: The Dps family members constitute a distinct group of multimeric and ferritin-like iron binding proteins (up to 500 iron atoms/12-mer) that are widespread in eubacteria and archaea and implicated in oxidative stress resistance and virulence. Despite the wealth of structural knowledge, the mechanism of iron incorporation has remained elusive. Here, we provide evidence on Dpr of the swine and human pathogen Streptococcus suis that: (i) iron incorporation proceeds by Fe(II) binding, Fe(II) oxidation and subsequent storage as Fe(III); (ii) Fe(II) atoms enter the 12-mer cavity through four hydrophilic pores; and (iii) Fe(II) atoms are oxidized inside the 12-mer cavity at 12 identical inter-subunit sites, which are structurally different but functionally equivalent to the ferroxidase centres of classical ferritins. We also provide evidence, by deleting and ectopically overexpressing Dpr, that Dpr affects cellular iron homeostasis. The key residues responsible for iron incorporation in S. suis Dpr are well conserved throughout the Dps family. A model for the iron incorporation mechanism of the Dps/Dpr ferritin-like protein is proposed.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland. arto.pulliainen@utu.fi
authors.forename: Arto T
authors.initials: AT
authors.lastname: Pulliainen
authors.forename: Anni
authors.initials: A
authors.lastname: Kauko
authors.forename: Sauli
authors.initials: S
authors.lastname: Haataja
authors.forename: Anastassios C
authors.initials: AC
authors.lastname: Papageorgiou
authors.forename: Jukka
authors.initials: J
authors.lastname: Finne
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D011487:Protein Conformation; D013291:Streptococcus / Q000187:drug effects / Q000378:metabolism*; D014867:Water / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C414750:Dpr protein, Streptococcus; D014867:Water; D005293:Ferritins; D007501:Iron