Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.

Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.

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The pathology associated with malaria infection is largely due to the ability of infected human RBCs to adhere to a number of receptors on endothelial cells within tissues and organs.This phenomenon is driven by the export of parasite-encoded proteins to the host cell, the exact function of many of which is still unknown.Here we inactivate the function of one of these exported proteins, PFA66, a member of the J-domain protein family.

Although parasites lacking this protein were still able to grow in cell 7 Colors Plaque LED Night Light culture, we observed severe defects in normal host cell modification, including aberrant morphology of surface knobs, disrupted presentation of the cytoadherence molecule PfEMP1, and a total lack of cytoadherence, despite the presence of the knob associated protein KAHRP.Complementation assays demonstrate that an intact J-domain is required for recovery to a wild-type phenotype and suggest that Medical Mattresses PFA66 functions in concert with a HSP70 to carry out host cell modification.Strikingly, this HSP70 is likely to be of host origin.

ATPase assays on recombinant protein verify a functional interaction between PFA66 and residual host cell HSP70.Taken together, our data reveal a role for PFA66 in host cell modification, strongly implicate human HSP70s as being essential in this process and uncover a new KAHRP-independent molecular factor required for correct knob biogenesis.