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

Nyakundi, David O; Vuko, Loyiso A M; Bentley, Stephen J; Hoppe, Heinrich C; Blatch, Gregory L; Boshoff, Aileen

Title: Plasmodium falciparum Hep1 is required to prevent the self aggregation of PfHsp70-3
Creator: Nyakundi, David O
Creator: Vuko, Loyiso A M
Creator: Bentley, Stephen J
Creator: Hoppe, Heinrich C
Creator: Blatch, Gregory L
Creator: Boshoff, Aileen
Date Issued: 2016
Date: 2016
Type: text
Type: article
Identifier: http://hdl.handle.net/10962/66109
Identifier: vital:28903
Identifier: https://doi.org/10.1371/journal.pone.0156446
Description: publisher version
Description: 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.
Description: This work was funded by grants from the National Research Foundation (NRF); grant number 87663 and Deutsche Forschungsgemeinschaft (DFG); grant number LI 402/14-1. D.O.N. is the recipient of academic development and training funds from Mwenge Catholic University, Moshi, Tanzania. S.J.B. is the recipient of an NRF Doctoral Innovation Scholarship.
Format: 13 pages
Format: pdf
Language: English
Relation: PLOS ONE
Relation: Nyakundi, D.O., Vuko, L.A.M., Bentley, S.J., Hoppe, H., Blatch, G.L., Boshoff, A. (2016) Plasmodium falciparum Hep1 Is Required to Prevent the Self Aggregation of PfHsp70-3. PLoS ONE 11(6): e0156446. doi:10.1371/journal.pone.0156446
Relation: PLOS ONE volume 11 number 6 1 13 June 2016 1932-6203
Rights: Copyright held by the authors
Rights: Use of this resource is governed by the terms and conditions of the PLOS ONE Open Access Statement (http://journals.plos.org/plosone/s/journal-information#loc-open-access)

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Boshoff, Aileen (Assoc Prof)

Hoppe, Heinrich C (Prof)

RU Department of Biochemistry, Microbiology and Bioinformatics

SDG 03. Good Health and Well-Being

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