title: Calmodulin regulates dimerization, motility, and lipid binding 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 motility are unknown. Here we show that binding of a single calmodulin causes the motor to adopt a monomeric state and to move actin filaments. In the absence of calmodulin, nonmotile dimers that cross-linked actin filaments were formed. Unexpectedly, structural analysis revealed that the dimerization domains include the calmodulin-binding neck region, essential for the generation of force and movement in myosins. Furthermore, monomeric myosin XXI bound to mixed liposomes, whereas the dimers did not. Lipid-binding sections overlapped with the dimerization domains, but also included a phox-homology domain in the converter region. We propose a mechanism of myosin regulation where dimerization, motility, and lipid binding are regulated by calmodulin. Although myosin-XXI dimers might act as nonmotile actin cross-linkers, the calmodulin-binding monomers might transport lipid cargo in the parasite.
authors.affiliation: Department of Cellular Physiology and Center for Nanosciences, Ludwig-Maximilians-Universität München, 80336 München, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Batters
authors.forename: Heike
authors.initials: H
authors.lastname: Ellrich
authors.forename: Constanze
authors.initials: C
authors.lastname: Helbig
authors.forename: Katy Anna
authors.initials: KA
authors.lastname: Woodall
authors.forename: Christian
authors.initials: C
authors.lastname: Hundschell
authors.forename: Dario
authors.initials: D
authors.lastname: Brack
authors.forename: Claudia
authors.initials: C
authors.lastname: Veigel
mesh_terms: D019540:Area Under Curve; D016367:Baculoviridae; D002147:Calmodulin / Q000378:metabolism*; D019281:Dimerization; D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D007891:Leishmania / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D009068:Movement; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics; D010743:Phospholipids / Q000378:metabolism*; D010957:Plasmids; D011487:Protein Conformation
chemical_list: D002147:Calmodulin; D009841:Oligonucleotides; D010743:Phospholipids; D009218:Myosins
keywords: motor properties; unconventional myosin