Heat shock protein 90 (Hsp90) is essential for the development of the main malaria agent, Plasmodium falciparum. Inhibitors that target Hsp90 function are known to not only kill the parasite, but also reverse resistance of the parasite to traditional antimalarials such as chloroquine. For this reason, Hsp90 has been tagged as a promising antimalarial drug target. As a molecular chaperone, Hsp90 facilitates folding of proteins such as steroid hormone receptors and kinases implicated in cell cycle and development. Central to Hsp90 function is its regulation by several co-chaperones. Various co-chaperones interact with Hsp90 to modulate its co-operation with other molecular chaperones such as Hsp70 and to regulate its interaction with substrates. The role of Hsp90 in the development of malaria parasites continues to receive research attention, and several Hsp90 co-chaperones have been mapped out. Recently, focus has shifted to P. falciparum R2TP proteins, which are thought to couple Hsp90 to a diverse set of client proteins. R2TP proteins are generally known to form a complex with Hsp90, and this complex drives multiple cellular processes central to signal transduction and cell division. Given the central role that the R2TP complex may play, the current review highlights the structure-function features of Hsp90 relative to R2TPs of P. falciparum.
Keywords: Heat shock protein 90; Plasmodium falciparum; R2TP proteins.