title: Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers.
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.
authors.affiliation: Howard Hughes Medical Institute, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110, USA.
authors.forename: Vasant
authors.initials: V
authors.lastname: Muralidharan
authors.forename: Anna
authors.initials: A
authors.lastname: Oksman
authors.forename: Priya
authors.initials: P
authors.lastname: Pal
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Goldberg
mesh_terms: D001216:Asparagine; D018835:Chaperonin 10 / Q000502:physiology*; D005334:Fever / Q000378:metabolism / Q000469:parasitology* / Q000503:physiopathology; D055785:Gene Knockdown Techniques; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000469:parasitology / Q000503:physiopathology; D010641:Phenotype; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000502:physiology*; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics / Q000502:physiology
chemical_list: D018835:Chaperonin 10; D020543:Proteome; D015800:Protozoan Proteins; D001216:Asparagine