title: Plasmodium falciparum Hep1 Is Required to Prevent the Self Aggregation of PfHsp70-3.
abstract: 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.
authors.affiliation: Biotechnology Innovation Centre, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: David O
authors.initials: DO
authors.lastname: Nyakundi
authors.affiliation: Biotechnology Innovation Centre, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: Loyiso A M
authors.initials: LA
authors.lastname: Vuko
authors.affiliation: Biotechnology Innovation Centre, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Bentley
authors.affiliation: Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hoppe
authors.affiliation: Biomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa.|College of Health and Biomedicine, Victoria University, Melbourne, Victoria 8001, Australia.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
authors.affiliation: Biotechnology Innovation Centre, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: Aileen
authors.initials: A
authors.lastname: Boshoff
mesh_terms: D003600:Cytosol; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology; D008928:Mitochondria / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity; D066263:Protein Aggregation, Pathological / Q000235:genetics; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D015800:Protozoan Proteins