Plasmodium falciparum Myosin B is a slow motor optimized for force generation

Robblee, J. P.; Moussaoui, D.; Bookwalter, C. S.; Auguin, D.; Fagnant, P. M.; MacFarlane, J. E.; Previs, M. J.; Houdusse, A.; Trybus, K. M.; Robert-Paganin, J.

doi:10.64898/2026.09.11.750570

bioRxiv · 10.64898/2026.09.11.750570

Plasmodium falciparum Myosin B is a slow motor optimized for force generation

Robblee, J. P.·Moussaoui, D.·Bookwalter, C. S.·Auguin, D.·Fagnant, P. M.·MacFarlane, J. E.·Previs, M. J.·Houdusse, A.·Trybus, K. M.·Robert-Paganin, J.

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Abstract

Malaria is a disease caused by apicomplexan parasites of the genus Plasmodium. These organisms express two atypical class-XIV myosins: Myosin A (MyoA), a core component of the glideosome expressed throughout the entire lifecycle, and Myosin B (MyoB), which is restricted to invasive stages and localizes to the apical region. Here, we determine the crystal structure of Plasmodium falciparum MyoB (PfMyoB) in the Rigor state and identify its essential light chain as the same subunit bound to MyoA. Combining structural analysis, molecular dynamics simulations and in vitro kinetic and motility assays, we show that PfMyoB is a slow motor optimized for force production during invasion. The N-terminal extensions of PfMyoA and PfMyoB exert distinct effects on each motor s mechanochemistry. Altogether, these findings reveal how Plasmodium myosins have evolved specialized functions during the complex parasite lifecycle and provide insight into developing multi-target inhibitors of erythrocytic invasion based on the PfMyoA inhibitor KNX-002.

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Robblee, J. P., Moussaoui, D., Bookwalter, C. S., Auguin, D., Fagnant, P. M., MacFarlane, J. E., Previs, M. J., Houdusse, A., Trybus, K. M., Robert-Paganin, J.. 2026-09-12. Plasmodium falciparum Myosin B is a slow motor optimized for force generation. https://doi.org/10.64898/2026.09.11.750570

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