Department of Cellular Physiology and Center for Nanosciences, Ludwig-Maximilians-Universität München, 80336 München, Germany.
Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):E227-36. doi: 10.1073/pnas.1319285110. Epub 2013 Dec 30.
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.
肌球蛋白 XXI 是唯一在利什曼原虫寄生虫中表达的肌球蛋白。尽管人们假设它执行各种运动功能，但运动的聚合状态、货物结合和运动状态尚不清楚。在这里，我们表明，单个钙调蛋白的结合导致马达采用单体状态并移动肌动蛋白丝。在没有钙调蛋白的情况下，形成了交联肌动蛋白丝的非运动二聚体。出乎意料的是，结构分析表明，二聚化结构域包括钙调蛋白结合颈区，这对于肌球蛋白产生力和运动是必不可少的。此外，单体肌球蛋白 XXI 结合到混合脂质体上，而二聚体则不结合。脂质结合部分与二聚化结构域重叠，但也包括在转换器区域中的 PHox 同源结构域。我们提出了一种肌球蛋白调节机制，其中钙调蛋白调节二聚化、运动和脂质结合。尽管肌球蛋白-XXI 二聚体可能作为非运动肌动蛋白交联剂起作用，但钙调蛋白结合的单体可能在寄生虫中运输脂质货物。
