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The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x

Daniyan, MO, Boshoff, A, Prinsloo, E, Pesce, ER and Blatch, Gregory ORCID: 0000-0003-0778-8577 (2016) The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x. PLoS ONE, 11 (2). ISSN 1932-6203

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Abstract

Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentrationdependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria.

Item Type: Article
Uncontrolled Keywords: malaria; plasmodium falciparum; molecular chaperones; heat shock protein 70; heat shock protein 40; protein aggregation; protein binding
Subjects: FOR Classification > 1101 Medical Biochemistry and Metabolomics
FOR Classification > 1108 Medical Microbiology
Faculty/School/Research Centre/Department > College of Health and Biomedicine
Depositing User: Symplectic Elements
Date Deposited: 17 Sep 2017 23:59
Last Modified: 20 Sep 2017 03:41
URI: http://vuir.vu.edu.au/id/eprint/34515
DOI: https://doi.org/10.1371/journal.pone.0148517
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Citations in Scopus: 9 - View on Scopus

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