Plasmodium falciparum Hsp70–Hsp90 organising protein complexed to ADP (Johnson et al. 1998). It seems in the presence of added ATP, less PfHsp90 was part of the PfHsp70 complex than was involved in the formation of this complex in the absence of added ATP (Fig 5b). Thus, ATP may have inhibited the association between PfHsp70 and PfHop, resulting in less PfHsp90 protein associating with PfHsp70. It seems that the possible association between PfHop and PfHsp70 (Fig. 5b) was sensitive to nucleotide, suggesting that PfHop and PfHsp70's associa- tion represents a functional interaction. A study by Famin and Ginsburg (2003), observed that PfHsp70 and PfHsp90 both associate with ferriprotopor- phyrin IX, a receptor of chloroquine that accumulates in chloroquine treated parasites. Ferriprotoporphyrin IX is thought to modulate the susceptibility of the parasite to chloroquine (Fitch 1989). This suggests that PfHsp70 and PfHsp90 may jointly facilitate the folding of proteins of parasitic origin that are implicated in regulating antimalarial drug efficacy. Interestingly, PfHsp90, PfHsp70 and PfHop were previously found to be distinctly upregulated in a group of clinical malaria patients (Pallavi et al. 2010). This suggests that the expression of these proteins may share a common regulatory trigger, and that their expression correlates with clinical malaria progression. As further evidence of their important role, plasmodial heat shock proteins have been described as potential antimalarial drug targets (reviewed in Pesce et al. (2010) and Shonhai (2010). Plasmodial heat shock proteins may be targeted in combination therapies by developing drugs that target these molecules and other malarial protein drug targets that fold through pathways that are facilitated by the parasite's chaperone machinery (reviewed in Pesce et al. 2010; Shonhai 2010). The possible role of PfHop in coordinating the PfHsp70– PfHsp90 functional pathway might lead to interesting prospects in the search for alternative antimalarial therapies. For example, some pyrimidinones with antimalarial activity and are known to bind to the EEVD motif of Hsp70. These compounds may be able to inhibit interaction of Hsp70 with its co-chaperones such as Hop, Hsp40 and client substrates (Shonhai 2010). Thus, an understanding of the PfHop mediation of PfHsp70–PfHsp90 pathway could present a potential antimalarial drug target. This is particularly an important pathway to target, as inhibition of the Hsp70–Hsp90 pathway is known to lead to degradation of client proteins that depend on this pathway for folding (Whitesell and Lindquist 2005). Since both PfHsp70 and Hsp90 play essential roles in the folding of malarial proteins (Pavithra et al. 2007; Shonhai et al. 2007), targeting this pathway has conceivable deleterious effects to the parasite. In conclusion, we have provided evidence that PfHop potentially exists in association with PfHsp70 and PfHsp90. 201 Further studies need to be undertaken in order to under- stand the mechanism by which PfHop modulates this pathway in the malaria parasite and to understand if there may be variations between the two pathways in the host and malaria parasite towards the development of possible malaria intervention strategies. Acknowledgements AS, GLB and JMP were in part supported by the DFG “German–African Cooperation Projects in Infectology” programme (Li402/12-1), which also supported GWG and PM as postgraduate students. Further funding to support this study was provided by the University of Zululand Research Committee. This work was supported in part by an equipment grant provided to AS by the Department of Science and Technology/National Research Foundation (NRF) of South Africa. 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