Structure of the Dps-Like Protein from Sulfolobus Solfataricus Reveals a Bacterioferritin-Like Dimetal Binding Site within a Dps-Like Dodecameric Assembly.

摘要: Oxidative stress, in which reactive oxygen species (ROS1) react indiscriminately with DNA, proteins and lipids, is a universal phenomenon experienced by organisms all domains of life. Cumulative damage from ROS now thought to contribute numerous disease states multitude reports the primary literature describe role oxidative stress human diseases. Thus, understanding molecular responses significant medical importance. Although much work has been done characterize management eukaryotes bacteria, response archaea poorly understood. However, elucidation protective mechanisms utilized certain provide insight into diversity across life. Numerous have evolved minimize repair damaging effects ROS. These include enzymes such as superoxide dismutase reductase, convert ion (O2) and/or hydrogen peroxide (H2O2). Hydrogen generated other ways well is, fact, natural product cell. relatively moderate oxidant, its interaction Fe2+ through Fenton reaction results production more destructive hydroxyl radical (eq I). The combination H2O2 thus represents lethal for life, elimination are essential. H2O2+Fe2+→Fe3++OH-+HO· (I) Catalase one means per destruction unwanted H2O2, where disproportionation water oxygen. An alternative strategy use various peroxidase activities, including glutathione thioredoxin dependent peroxidases, reduce H2O while avoiding oxygen. A third minimizing concentration free ferrous ion. This employed mineralization reactions catalyzed ferritin, bacterioferritin, DPS (DNA binding protein starved cells), members ferritin superfamily (1–3). In case at ferroxidase center, eventually leading deposition benign insoluble ferric oxide core within hollow, spherically shaped particles. DPS catalyzes similar reaction. contrast clearly prefers oxidant (4, 5). activity simultaneously mitigates toxicity 2-electron reduction form water, same time, it inactivates oxidation Fe3+. Recent indicates that bacterioferritin can also utilize an (5, 6); hence, will catalyze simultaneous consumption both reactants. The secondary tertiary structures molecules largely homologous those (7). structural these highly conserved four-helix bundle, composed two consecutive helix-turn-helix motifs. motifs related each pseudo 2-fold symmetry connected extended loop runs length four helix bundle. structurally characterized proteins, fifth found this loop, helps define symmetric subunit interface (7–9). Although DPS, serve protect organism sequestering intracellular iron, active site iron bound oxidized different bacterioferritin. di-iron carboxylate motif located contrast, show between subunits 10, 11). A second difference nature their oligomeric assemblies. While typically 24-mers, 432 point group symmetry, dodecamer (12-mer), 23 (7). We previously reported isolation characterization DPS-like (DPSL) Sulfolobus solfataricus (SsDPSL) (12) Pyrococcus furiosus (13) described antioxidant vitro. On basis phylogenetic analysis, along eight others, were shown monophyletic cluster distinct subclasses superfamily. Biochemical DPSL reveals dodecameric assemblies preferentially controlled (12), N-terminal extension present molecules, analogy, mediate DNA. observed properties, state, prototypical solfataricus, subclass was termed (12). To date, center less clear. Analogous authentic candidate residues intersubunit suggested (12). corresponding bacterioferritin-like sequences (13). not surprising classified Pfam (14) subfamily (CD 1052.2) lacks involved heme binding. Given extensive biochemical similarities functional properties responsible preservation signature diverse prokaryotes unclear. So too itself. effort illuminate signature, we undertaken studies proteins. Here, structure SsDPSL, hyperthermophilic archaeon solfataricus.