title: Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion.
abstract: The role of molecular chaperones, among them heat shock proteins (Hsps), in the development of malaria parasites has been well documented. Hsp70s are molecular chaperones that facilitate protein folding. Hsp70 proteins are composed of an N-terminal nucleotide binding domain (NBD), which confers them with ATPase activity and a C-terminal substrate binding domain (SBD). In the ADP-bound state, Hsp70 possesses high affinity for substrate and releases the folded substrate when it is bound to ATP. The two domains are connected by a conserved linker segment. Hsp110 proteins possess an extended lid segment, a feature that distinguishes them from canonical Hsp70s. Plasmodium falciparum Hsp70-z (PfHsp70-z) is a member of the Hsp110 family of Hsp70-like proteins. PfHsp70-z is essential for survival of malaria parasites and is thought to play an important role as a molecular chaperone and nucleotide exchange factor of its cytosolic canonical Hsp70 counterpart, PfHsp70-1. Unlike PfHsp70-1 whose functions are fairly well established, the structure-function features of PfHsp70-z remain to be fully elucidated. In the current study, we established that PfHsp70-z possesses independent chaperone activity. In fact, PfHsp70-z appears to be marginally more effective in suppressing protein aggregation than its cytosol-localized partner, PfHsp70-1. Furthermore, based on coimmunoaffinity chromatography and surface plasmon resonance analyses, PfHsp70-z associated with PfHsp70-1 in a nucleotide-dependent fashion. Our findings suggest that besides serving as a molecular chaperone, PfHsp70-z could facilitate the nucleotide exchange function of PfHsp70-1. These dual functions explain why it is essential for parasite survival.
authors.affiliation: Department of Biochemistry, University of Venda, Private Bag X5050, Thohoyandou, 0950, South Africa.
authors.forename: Tawanda
authors.initials: T
authors.lastname: Zininga
authors.affiliation: Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, 2050, South Africa.
authors.forename: Ikechukwu
authors.initials: I
authors.lastname: Achilonu
authors.affiliation: Department of Biochemistry and Microbiology, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hoppe
authors.affiliation: Biotechnology Innovation Centre, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa.
authors.forename: Earl
authors.initials: E
authors.lastname: Prinsloo
authors.affiliation: Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, 2050, South Africa.
authors.forename: Heini W
authors.initials: HW
authors.lastname: Dirr
authors.affiliation: Department of Biochemistry, University of Venda, Private Bag X5050, Thohoyandou, 0950, South Africa. addmore.shonhai@univen.ac.za.
authors.forename: Addmore
authors.initials: A
authors.lastname: Shonhai
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology; D018832:Molecular Chaperones; D009711:Nucleotides / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity; D000072417:Protein Domains / Q000235:genetics; D017510:Protein Folding
chemical_list: D050957:HSP110 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D018832:Molecular Chaperones; D009711:Nucleotides; D000251:Adenosine Triphosphatases
keywords: Chaperone; Malaria; Nucleotide exchange factor; PfHsp70-z; Plasmodium falciparum; Protein aggregation