Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3

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Nyakundi, David O, Vuko, Loyiso AM, Bentley, Stephen J, Hoppe, Heinrich, Blatch, Gregory ORCID: 0000-0003-0778-8577 and Boshoff, Aileen (2016) Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3. PLoS ONE, 11 (6). ISSN 1932-6203


The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria.

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Item type Article
DOI 10.1371/journal.pone.0156446
Official URL
Subjects Historical > FOR Classification > 1101 Medical Biochemistry and Metabolomics
Current > Division/Research > College of Health and Biomedicine
Keywords malaria treatment; cytosol; mitochondria; molecular chaperones; protein aggregation; Hsp70 protein; PfHep1
Citations in Scopus 8 - View on Scopus
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