Plasmodium Falciparum Heat Shock Protein 110 Stabilizes the Asparagine Repeat-Rich Parasite Proteome During Malarial Fevers

Nat Commun. 2012;3:1310. doi: 10.1038/ncomms2306.

Abstract

One-fourth of Plasmodium falciparum proteins have asparagine repeats that increase the propensity for aggregation, especially at elevated temperatures that occur routinely in malaria-infected patients. Here we report that a Plasmodium Asn repeat-containing protein (PFI1155w) formed aggregates in mammalian cells at febrile temperatures, as did a yeast Asn/Gln-rich protein (Sup35). Co-expression of the cytoplasmic P. falciparum heat shock protein 110 (PfHsp110c) prevented aggregation. Human or yeast orthologs were much less effective. All-Asn and all-Gln versions of Sup35 were protected from aggregation by PfHsp110c, suggesting that this chaperone is not limited to handling runs of asparagine. PfHsp110c gene-knockout parasites were not viable and conditional knockdown parasites died slowly in the absence of protein-stabilizing ligand. When exposed to brief heat shock, these knockdowns were unable to prevent aggregation of PFI1155w or Sup35 and died rapidly. We conclude that PfHsp110c protects the parasite from harmful effects of its asparagine repeat-rich proteome during febrile episodes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asparagine
  • Chaperonin 10 / physiology*
  • Fever / metabolism
  • Fever / parasitology*
  • Fever / physiopathology
  • Gene Knockdown Techniques
  • Humans
  • Malaria, Falciparum / metabolism*
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / physiopathology
  • Phenotype
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism*
  • Plasmodium falciparum / physiology
  • Proteome / genetics*
  • Proteome / metabolism
  • Protozoan Proteins / physiology*
  • Repetitive Sequences, Amino Acid / genetics
  • Repetitive Sequences, Amino Acid / physiology

Substances

  • Chaperonin 10
  • Proteome
  • Protozoan Proteins
  • Asparagine