Calmodulin regulates dimerization, motility, and lipidbinding of Leishmania myosin XXI

Abstract

Myosin XXI is the only myosin expressed in Leishmania parasites.Although it is assumed that it performs a variety of motile functions, the motor's oligomerization states, cargo-binding, and mo-tility are unknown. Here we show that binding of a singlecalmodulin causes the motor to adopt a monomeric state and tomove actin filaments. In the absence of calmodulin, nonmotiledimers that cross-linked actin filaments were formed. Unexpectedly, structural analysis revealed that the dimerization domainsinclude the calmodulin-binding neck region, essential for the generation of force and movement in myosins. Furthermore, mono-meric myosin XXI bound to mixed liposomes, whereas the dimersdid not. Lipid-binding sections overlapped with the dimerizationdomains, but also included a phox-homology domain in the converter region. We propose a mechanism of myosin regulationwhere dimerization, motility, and lipid binding are regulated bycalmodulin. Although myosin-XXI dimers might act as nonmotileactin cross-linkers, the calmodulin-binding monomers might transport lipid cargo in the parasite.