eprintid: 18758 rev_number: 33 userid: 1419 dir: disk0/00/01/87/58 datestamp: 2013-05-28 15:41:27 lastmod: 2021-02-05 19:50:50 status_changed: 2013-05-28 15:41:27 type: article metadata_visibility: show item_issues_count: 0 eprint_status: archive creators_name: Botha, M creators_name: Chiang, AN creators_name: Needham, PB creators_name: Stephens, LL creators_name: Hoppe, HC creators_name: Külzer, S creators_name: Przyborski, JM creators_name: Lingelbach, K creators_name: Wipf, P creators_name: Brodsky, JL creators_name: Shonhai, A creators_name: Blatch, GL creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: pwipf@pitt.edu creators_email: jbrodsky@pitt.edu creators_email: creators_email: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: PWIPF creators_id: JBRODSKY creators_id: creators_id: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: creators_orcid: 0000-0002-6984-8486 creators_orcid: creators_orcid: title: Plasmodium falciparum encodes a single cytosolic type i Hsp40 that functionally interacts with Hsp70 and is upregulated by heat shock ispublished: pub divisions: sch_as_chemistry full_text_status: public abstract: 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. date: 2011-07-01 date_type: published publication: Cell Stress and Chaperones volume: 16 number: 4 pagerange: 389 - 401 refereed: TRUE issn: 1355-8145 id_number: 10.1007/s12192-010-0250-6 other_id: NLM PMC3118825 pmcid: PMC3118825 pmid: 21191678 mesh_headings: Adenosine Triphosphatases--metabolism mesh_headings: Cytosol--metabolism mesh_headings: Gene Expression mesh_headings: HSP40 Heat-Shock Proteins--metabolism mesh_headings: HSP70 Heat-Shock Proteins--metabolism mesh_headings: Heat-Shock Response mesh_headings: Hydrolysis mesh_headings: Molecular Chaperones--metabolism mesh_headings: Plasmodium falciparum--genetics mesh_headings: Plasmodium falciparum--metabolism mesh_headings: Up-Regulation chemical_names: HSP40 Heat-Shock Proteins chemical_names: HSP70 Heat-Shock Proteins chemical_names: Molecular Chaperones chemical_names: Adenosine Triphosphatases citation: 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 document_url: http://d-scholarship-dev.library.pitt.edu/18758/3/12192_2010_Article_250.pdf document_url: http://d-scholarship-dev.library.pitt.edu/18758/1/licence.txt