A genome-wide chromatin-associated nuclear peroxiredoxin from the malaria parasite Plasmodium falciparum

J Biol Chem. 2011 Apr 1;286(13):11746-55. doi: 10.1074/jbc.M110.198499. Epub 2011 Jan 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / enzymology*
  • Chromatin / genetics
  • Genome-Wide Association Study / methods
  • Glutaredoxins / genetics
  • Glutaredoxins / metabolism
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Peroxiredoxins / genetics
  • Peroxiredoxins / metabolism*
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / genetics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Substrate Specificity
  • Thioredoxins / genetics
  • Thioredoxins / metabolism

Substances

  • Chromatin
  • Glutaredoxins
  • Nuclear Proteins
  • Protozoan Proteins
  • Thioredoxins
  • Peroxiredoxins