Plasmodium falciparum heat shock protein 110stabilizes the asparagine repeat-rich parasiteproteome during malarial fevers

摘要

One-fourth of Plasmodium falciparum proteins have asparagine repeats that increase thepropensity for aggregation, especially at elevated temperatures that occur routinely inmalaria-infected patients. Here we report that a Plasmodium Asn repeat-containing protein(PFI1155w) formed aggregates in mammalian cells at febrile temperatures, as did a yeastAsn/Gln-rich protein (Sup35). Co-expression of the cytoplasmic P. falciparum heat shockprotein 110 (PfHsp110c) prevented aggregation. Human or yeast orthologs were much lesseffective. All-Asn and all-Gln versions of Sup35 were protected from aggregation byPfHsp110c, suggesting that this chaperone is not limited to handling runs of asparagine.PfHsp110c gene-knockout parasites were not viable and conditional knockdown parasites diedslowly in the absence of protein-stabilizing ligand. When exposed to brief heat shock, theseknockdowns were unable to prevent aggregation of PFI1155w or Sup35 and died rapidly. Weconclude that PfHsp110c protects the parasite from harmful effects of its asparagine repeatrich proteome during febrile episodes.