15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function.
Heat shock proteins are essential for the survival of all cells. The C-terminal EEVD motif of Hsp70 has previously been implicated in binding 15-deoxyspergualin (DSG), an immunosuppressant with antimalarial activity whose mechanism of action is uncertain. We report the cloning, overexpression, and characterization of three members of the heat shock family, PfHsp70-1 (an Hsp70 protein with a C-terminal EEVD motif), PfHsp70-2 (an Hsp70 protein without the EEVD motif), and PfHsp70 interacting protein. The chaperone activity of PfHsp70-1, and PfHsp70-2 was enhanced by ATP and by PfHip. Interestingly, while binding of protein substrates to PfHsp70-1, PfHsp70-2 and PfHip was unaffected in the presence of DSG, the ATP enhanced chaperone activity of PfHsp70-1 but not PfHsp70-2 was stimulated further by DSG. Our finding suggests that the binding partner of DSG in the parasite cellular milieu is PfHsp70-1 and paves the way for the elucidation of the mechanism of antimalarial action of DSG.
Ramya
T N C
TN
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
Surolia
Namita
N
Surolia
Avadhesha
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D006146:Guanidines / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008027:Light; D018832:Molecular Chaperones / Q000187:drug effects / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects*; D012542:Scattering, Radiation
D006146:Guanidines; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D000255:Adenosine Triphosphate; C037258:gusperimus