title: A genome-wide chromatin-associated nuclear peroxiredoxin from the malaria parasite Plasmodium falciparum.
abstract: Malaria parasites are subjected to high levels of oxidative stress during their development inside erythrocytes and the ability of the parasite to defend itself against this assault is critical to its survival. Therefore, Plasmodium possesses an effective antioxidant defense system that could potentially be used as a target for the development of inhibitor-based therapy. We have identified an unusual peroxiredoxin protein that localizes to the nucleus of Plasmodium falciparum and have renamed it PfnPrx (PF10_0268, earlier called MCP1). Our work reveals that PfnPrx has a broad specificity of substrate being able to utilize thioredoxin and glutaredoxin as reductants and having the ability to reduce simple and complex peroxides. Intriguingly, chromatin immunoprecipitation followed by deep sequencing reveals that the enzyme associates with chromatin in a genome-wide manner with a slight enrichment in coding regions. Our results represent the first description of a dedicated chromatin-associated peroxiredoxin and potentially represent an ingenious way by which the parasite can survive the highly oxidative environment within its human host.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Dave
authors.initials: D
authors.lastname: Richard
authors.forename: Richard
authors.initials: R
authors.lastname: Bartfai
authors.forename: Jennifer
authors.initials: J
authors.lastname: Volz
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Ralph
authors.forename: Sylke
authors.initials: S
authors.lastname: Muller
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D002843:Chromatin / Q000201:enzymology* / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D054477:Glutaredoxins; D009687:Nuclear Proteins; D015800:Protozoan Proteins; D013879:Thioredoxins; D054464:Peroxiredoxins