Karakterisering av metallregulatorernas struktur och funktion i en aktinomycetmodell – proteiner med en nyckelroll i metallhomeostas och hantering av oxidativ stress
Tidsperiod: 2017-01-01 till 2020-12-31
Projektledare: Julia Johanna Griese
Bidragstyp: Bidrag för anställning eller stipendier
Budget: 2 800 000 SEK
Metal ions are essential for life, as structural components of the cellular machinery and catalysts of chemical reactions, yet are toxic at high concentrations. Metal homeostasis is therefore tightly controlled in order to prevent deficits, while avoiding equally harmful excess. Iron and manganese are two of the most commonly used metal ions in protein cofactors. While Fe readily reacts with reactive oxygen species, damaging cellular components, Mn protects cells against oxidative damage. Consequently Mn and Fe homeostasis are closely integrated and coordinated with the oxidative stress response. This regulatory network has a profound influence on cellular metabolism and plays an important role in virulence of bacterial pathogens, but the underlying mechanisms are poorly understood. I will therefore structurally, biochemically, and functionally characterise the Mn, Fe and peroxide-responsive transcription factors that regulate metal homeostasis and the oxidative stress response in Saccharopolyspora erythraea. This actinomycete is an ideal model organism for the purpose because it requires both Mn and Fe, in contrast to current model organisms whose metabolism is either Fe or Mn-centric. The results from this project will form the basis for unravelling the metal regulatory network in actinomycetes, while also shedding more light on the fundamental question of how proteins differentiate between Mn and Fe.