POSTPONED- Structural studies on the Plasmodium falciparum myosins: search for inhibitors to stop parasite invasion - Postponed
Malaria is the deadliest parasitic disease (0.5 million deaths per year) and results from infection by Apicomplexan parasites from the genus Plasmodium. PfMyoA, an atypical class XIV myosin from Plasmodium falciparum, is essential both for parasite motility and infectivity. In this work, we combined X-ray crystallography, transient kinetics and molecular dynamics to decipher the specificities of this motor. PfMyoA comprises an atypical N-terminal extension that acts as a switch allowing the motor to move at high speed when the extension is phosphorylated (during motile stages) or to produce more force when dephosphorylated (during invasion). The full-length structures of PfMyoA reveal that the specific light chains are involved in the stabilization of a more primed pre-power stroke through unforeseen motor domain/lever arm interactions. Altogether, these results define PfMyoA as a first order target to design a new generation of antimalarial compounds able to block motor function, association to PfAct1 or light-chains targeting to the lever arm.
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