Plasmodium falciparum Hsp70–Hsp90 organising protein 197 Fig. 2 PfHop model displays surface exposed residues implicated in interaction with PfHsp70 and PfHsp90. Schematic representation of PfHop showing the TPR domain as indicated by rectangles highlight- ed in grey. The numbers represent the starting and the ending amino acid residues of the three TPR domains. Ribbon representation of the three dimensional models of TPR1, TPR2A and TPR2B domains. experiment was repeated without adding ATP to the lysate (lane ‘−ATP’, Fig. 5b). Hop associates preferably with Hsp70 when the latter is bound to ADP. In the absence of added ATP, it likely that most of the PfHsp70 protein in the lysate was either bound to ADP or was in a nucleotide-free state. In the absence of added ATP, PfHsp70 immunopre- cipitated along with PfHop (lane ‘−ATP’, Fig. 5b). When ATP was added to the lysate, we could not detect PfHop in the PfHsp70 complex (lane ‘+ATP’, Fig. 5b). PfHsp90 was detected when its association with PfHsp70 was investigat- ed both in the presence and absence of added ATP. PfHsp90 appeared on the Western blot as a species of approximately 90 kDa (Fig. 5b). However, in the absence of ATP, more PfHsp90 protein associated with PfHsp70 than when ATP was added to the parasite lysate (Fig. 5b). Discussion PfHsp70 and PfHsp90 chaperones of Plasmodium spp. are known to play essential roles in the development of the parasites. PfHsp70 and PfHsp90 have been characterised extensively and their roles in the development of P. falciparum are well documented (Banumathy et al. 2003; Sharma 1992; Shonhai et al. 2005; 2007). It is likely that these chaperones are functionally linked. In mammals, the TPR-rich Hop protein is known to modulate interaction of Hsp70 and Hsp90 chaperones. To the best of our Residues known to be crucial in the interaction of TPR1 and TPR2A with Hsp70 and Hsp90, respectively are represented in sticks. The models were generated by SWISS-MODEL (Arnold et al. 2006; Guex and Peitsch 1997; Schwede et al. 2003) and rendered using PyMol (DeLano 2002) knowledge, this is the first study to provide experimental evidence suggesting a possible role for the P. falciparum Hop homologue in mediating the functional partnership between PfHsp70 and PfHsp90. Based on bioinformatics analysis, PfHop possesses conserved TPR1 and TPR2A domains that are implicated in facilitating the interaction of Hop with Hsp70 and Hsp90 in mammalian cells (Fig. 1; Odunuga et al. 2003; 2004). Residues that have direct contact with Hsp70 and Hsp90 are conserved in PfHop and they protrude on the helical surfaces of the respective TPR domains (Fig. 2), thus positioning them for the possible interaction of PfHop with its chaperone clients. Overall, PfHop exhibits conserved structural features of a typical Hop protein. However, although most structural motifs are conserved in Hop proteins, it is interesting to note that plasmodial Hop proteins exhibit select distinct functional domains, com- pared to their counterparts of yeast and mammalian origin. The relative variations in sequences exhibited between plasmodial Hop proteins and their counterparts from mouse, human as well as yeast even in important domains such as TPR and DP motifs (Fig. 1), could represent potential functional variation in the Hop-mediated path- ways in these species. For example, DP repeats have been found to modulate Hop function by influencing the global folding status of Hop (Nelson et al. 2003) and thus variation within these domains could mirror functional specialisation of Hop proteins. It is thought that the less