Fig 7. A stepwise model for Plasmodium myosin force generation during merozoite invasion.

A PfMyoA produces force at three sequential energetic barriers to drive invasion. Successively more disruptive mutations bring the PfMyoA force production capacity closer to, or below, the energetic barriers, represented by orange bars with blurred tops indicating variability in individual parasites and RBCs. Some PfMyoA-K764E parasites fail at initiation of internalisation (Type C failures), some fail at completion of internalisation (Type B failures) and relatively few complete invasion. PfELC-cKO parasites often fail at the barrier of deformation (Type D failures), though some can deform and fail at initiation of internalisation (Type C failures). PfMyoA-cKO parasites never overcome the energetic barriers to deformation or internalisation. PfMyoB-cKO parasites are only impaired at initiation of internalisation, suggesting that PfMyoB may act to reduce the energetic barrier at initiation of internalisation. B Overview of actomyosin functions at each of the three steps, including using deformability to select suitable host cells, driving initial wrapping of the merozoite and twisting shut the invasion pore. Parasite effectors reduce the energetic barriers by modulating RBC biophysical properties, including creation of the tight junction (TJ) to introduce a line tension, insertion of membrane material (darker membrane) and binding of adhesins like EBA-175 that may affect RBC lipid packing C PfMyoA is phosphorylated before egress and may be dynamically dephosphorylated at some point before internalisation to tune the motor for maximal force production.