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Plasmodium falciparum encodes a single cytosolic type i Hsp40 that functionally interacts with Hsp70 and is upregulated by heat shock

Botha, M and Chiang, AN and Needham, PB and Stephens, LL and Hoppe, HC and Külzer, S and Przyborski, JM and Lingelbach, K and Wipf, P and Brodsky, JL and Shonhai, A and Blatch, GL (2011) Plasmodium falciparum encodes a single cytosolic type i Hsp40 that functionally interacts with Hsp70 and is upregulated by heat shock. Cell Stress and Chaperones, 16 (4). 389 - 401. ISSN 1355-8145

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Heat shock protein 70 (Hsp70) and heat shock protein 40 (Hsp40) function as molecular chaperones during the folding and trafficking of proteins within most cell types. However, the Hsp70-Hsp40 chaperone partnerships within the malaria parasite, Plasmodium falciparum, have not been elucidated. Only one of the 43 P. falciparum Hsp40s is predicted to be a cytosolic, canonical Hsp40 (termed PfHsp40) capable of interacting with the major cytosolic P. falciparum-encoded Hsp70, PfHsp70. Consistent with this hypothesis, we found that PfHsp40 is upregulated under heat shock conditions in a similar pattern to PfHsp70. In addition, PfHsp70 and PfHsp40 reside mainly in the parasite cytosol, as assessed using indirect immunofluorescence microscopy. Recombinant PfHsp40 stimulated the ATP hydrolytic rates of both PfHsp70 and human Hsp70 similar to other canonical Hsp40s of yeast (Ydj1) and human (Hdj2) origin. In contrast, the Hsp40-stimulated plasmodial and human Hsp70 ATPase activities were differentially inhibited in the presence of pyrimidinone-based small molecule modulators. To further probe the chaperone properties of PfHsp40, protein aggregation suppression assays were conducted. PfHsp40 alone suppressed protein aggregation, and cooperated with PfHsp70 to suppress aggregation. Together, these data represent the first cellular and biochemical evidence for a PfHsp70-PfHsp40 partnership in the malaria parasite, and furthermore that the plasmodial and human Hsp70-Hsp40 chaperones possess unique attributes that are differentially modulated by small molecules. © 2010 Cell Stress Society International.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Botha, M
Chiang, AN
Needham, PB
Stephens, LL
Hoppe, HC
Külzer, S
Przyborski, JM
Lingelbach, K
Wipf, Ppwipf@pitt.eduPWIPF
Brodsky, JLjbrodsky@pitt.eduJBRODSKY0000-0002-6984-8486
Shonhai, A
Blatch, GL
Date: 1 July 2011
Date Type: Publication
Journal or Publication Title: Cell Stress and Chaperones
Volume: 16
Number: 4
Page Range: 389 - 401
DOI or Unique Handle: 10.1007/s12192-010-0250-6
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 1355-8145
MeSH Headings: Adenosine Triphosphatases--metabolism; Cytosol--metabolism; Gene Expression; HSP40 Heat-Shock Proteins--metabolism; HSP70 Heat-Shock Proteins--metabolism; Heat-Shock Response; Hydrolysis; Molecular Chaperones--metabolism; Plasmodium falciparum--genetics; Plasmodium falciparum--metabolism; Up-Regulation
Other ID: NLM PMC3118825
PubMed Central ID: PMC3118825
PubMed ID: 21191678
Date Deposited: 28 May 2013 15:41
Last Modified: 05 Feb 2021 19:50


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