title: The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x.
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 concentration-dependent 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.
authors: Biomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa.|Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
authors: Michael O
authors: MO
authors: Daniyan
authors: Biotechnology Innovation Centre, Rhodes University, Grahamstown, South Africa.
authors: Aileen
authors: A
authors: Boshoff
authors: Biotechnology Innovation Centre, Rhodes University, Grahamstown, South Africa.
authors: Earl
authors: E
authors: Prinsloo
authors: Biomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa.|College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia.
authors: Eva-Rachele
authors: ER
authors: Pesce
authors: Biomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa.|College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia.
authors: Gregory L
authors: GL
authors: Blatch
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D016778:Malaria, Falciparum / Q000469:parasitology; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D066329:Protein Aggregates; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D066329:Protein Aggregates; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D013884:Thiosulfate Sulfurtransferase; D000251:Adenosine Triphosphatases