title: A histone-like protein of mycobacteria possesses ferritin superfamily protein-like activity and protects against DNA damage by Fenton reaction.
abstract: Iron is an essential metal for living organisms but its level must be strictly controlled in cells, because ferrous ion induces toxicity by generating highly active reactive oxygen, hydroxyl radicals, through the Fenton reaction. In addition, ferric ion shows low solubility under physiological conditions. To overcome these obstacles living organisms possess Ferritin superfamily proteins that are distributed in all three domains of life: bacteria, archaea, and eukaryotes. These proteins minimize hydroxyl radical formation by ferroxidase activity that converts Fe(2+) into Fe(3+) and sequesters iron by storing it as a mineral inside a protein cage. In this study, we discovered that mycobacterial DNA-binding protein 1 (MDP1), a histone-like protein, has similar activity to ferritin superfamily proteins. MDP1 prevented the Fenton reaction and protects DNA by the ferroxidase activity. The K(m) values of the ferroxidase activity by MDP1 of Mycobacterium bovis bacillus Calmette-Guérin (BCG-3007c), Mycobacterium tuberculosis (Rv2986c), and Mycobacterium leprae (ML1683; ML-LBP) were 0.292, 0.252, and 0.129 mM, respectively. Furthermore, one MDP1 molecule directly captured 81.4±19.1 iron atoms, suggesting the role of this protein in iron storage. This study describes for the first time a ferroxidase-iron storage protein outside of the ferritin superfamily proteins and the protective role of this bacterial protein from DNA damage.
authors.affiliation: Department of Bacteriology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takatsuka
authors.forename: Mayuko
authors.initials: M
authors.lastname: Osada-Oka
authors.forename: Eisuke F
authors.initials: EF
authors.lastname: Satoh
authors.forename: Kengo
authors.initials: K
authors.lastname: Kitadokoro
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishiuchi
authors.forename: Mamiko
authors.initials: M
authors.lastname: Niki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Inoue
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shimoji
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ogura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Anura
authors.initials: A
authors.lastname: Rambukkana
authors.forename: Sohkichi
authors.initials: S
authors.lastname: Matsumoto
mesh_terms: D002570:Ceruloplasmin / Q000378:metabolism; D004249:DNA Damage; D005293:Ferritins / Q000502:physiology*; D006657:Histones / Q000502:physiology*; D009161:Mycobacterium / Q000201:enzymology / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding
chemical_list: D006657:Histones; D005293:Ferritins; D002570:Ceruloplasmin