Malaria is a mosquito-borne parasitic disease transmitted by infected Anopheles mosquitoes. It is caused by Apicomplexan parasites of the genus Plasmodium . These parasites have a complex lifecycle, alternating between motile and invasive stages, and express a limited repertoire of six myosins. Both motility and pathogenesis of Plasmodium rely on an atypical class XIV myosin, myosin A (MyoA), which can be targeted by small molecules such as KNX-002 to inhibit parasite development. In contrast, the mechanism and precise functions of other Plasmodium myosins remain unknown. Here, we present the high-resolution crystal structure of Plasmodium falciparum Myosin B (PfMyoB), another class-XIV myosin implicated in erythrocytic invasion. Surprisingly, both the structure and the sequence of PfMyoB diverge significantly from PfMyoA, suggesting a distinct mechanism of force production. A combination of structural analyses and in vitro assays demonstrates that PfMyoB is a slow motor optimized to produce ensemble force, which consistent with its biological role. Altogether, these results reveal how Plasmodium myosins belonging to the same class have evolved differently to fulfill distinct physiological function. Finally, our work advances the understanding of allosteric communication in molecular motors.
Robblee et al. (Sun,) studied this question.