Hsp70-1 from Plasmodium falciparum: Protein stability, domain analysis and chaperone activity

P. falciparum contains six copies of the Hsp70 gene of which PfHsp70-1 is important in the parasite's lifecycle. The protein consists of two domains like other Hsp70s but has an unusually long C-terminal tail. The full-length protein is stable towards high temperatures and chemical denaturants. Fluorescence and circular dichroism studies demonstrate that the ∼ 42 kDa N-terminal/nucleotide-binding domain (NBD) is relatively unstable in isolation. Addition of the ∼ 35 kDa C-terminal domain with an extended tail containing an EEVD motif confers thermal stability and makes it less susceptible to thermal denaturation. This suggests that the C-terminal domain functions as a stabilization domain. PfHsp70-1 possesses a chaperone activity in addition to other functions reported earlier. We report that the chaperone activity of PfHsp70-1 is enhanced in the presence of P. falciparum Hsp40 (Pfj1, PFD0465w), the homolog of bacterial DnaJ. The present work represents the first evidence for functional interactions between the PfHsp70-1 and Pfj1.