Plasmodium falciparum Myosin F with a Rab-like tail domain localises to perinuclear membranes and associates with trafficking proteins

Members of the myosin superfamily are found in all eukaryotes, including Plasmodium falciparum, the parasite that causes malaria. Plasmodium falciparum expresses six myosins, but apart from PfMyoA, these motors remain largely uncharacterised. This includes the class XXII myosin PfMyoF. Here, we characterise PfMyoF using structural prediction tools, biochemical assays, and advanced imaging. We show that PfMyoF is a plus-end directed, processive motor with a long neck domain containing six IQ motifs that bind the calmodulin homologue PfCaM. PfMyoF can dimerise and is predicted to adopt an autoinhibited conformation via tail backfolding. The PfMyoF tail contains a Rab-like domain that has not been identified in any other known class of myosin. Pull-down experiments show interactions between endogenous PfMyoF and trafficking proteins, including the vesicle marker PfRab18. Expansion and immunoelectron microscopy reveal that PfMyoF localises to a perinuclear membrane compartment. Our findings define PfMyoF as the first known myosin with a Rab-like domain and highlight its potential role in parasite membrane trafficking pathways.