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.
Highlights
Plasmodium falciparum is the protozoan parasite responsible for the most virulent form of human malaria [1]
Bacteria cells expressing PFA0660w were harvested by centrifugation and the Functional Interaction of PFA0660w with PfHsp70-x cell pellet resuspended in lysis buffer (LB: 10 mM Tris-HCl, pH 8.5, 300 mM NaCl, 50 mM imidazole, 1 mM PMSF, 1 mg/ml lysozyme), allowed to stand for 20 min at room temperature and frozen at -80°C overnight
Most heat shock protein 40 (Hsp40) proteins have been found to exist as homodimers, and dimer formation has been shown to be important for functionality [48,49,50,51,52]
Summary
Plasmodium falciparum is the protozoan parasite responsible for the most virulent form of human malaria [1]. Preventable and often curable, malaria remains a life-threatening disease with high mortality [2,3,4]. Despite the use of preventative approaches such as insecticide treated nets and indoor residual spraying [5,6], chemotherapeutic intervention is still necessary to the effort to eradicate malaria. The ability of P. falciparum to develop drug resistance [7,8] has made the search for new pharmacotherapy an imperative.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
