Calmodulin regulates dimerization, motility, and lipid binding of Leishmania myosin XXI
Calmodulin regulates dimerization, motility, and lipid binding of Leishmania myosin XXI
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DOI：
10.1073/pnas.1319285110
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发表时间：
2014-01-14
影响因子：
11.1
通讯作者：
Veigel, Claudia
中科院分区：
文献类型：
--
作者：
Batters, Christopher;Ellrich, Heike;Veigel, Claudia
肌球蛋白XXI是利什曼原虫中唯一表达的肌球蛋白。虽然假设它执行各种运动功能，但马达的寡聚状态、货物结合和运动性是未知的。在这里，我们展示了单个钙调蛋白的结合导致马达采取单体状态并移动肌动蛋白细丝。在没有钙调素的情况下，形成了交联肌动蛋白细丝的非运动性二聚体。出乎意料的是，结构分析显示，二聚化结构域包括钙调蛋白结合颈区，这是肌球蛋白生成力和运动所必需的。此外，单体肌球蛋白XXI与混合脂质体结合，而二聚体不结合。脂质结合区与二聚化结构域重叠，但在转化区还包括一个光同源结构域。我们提出了一种肌球蛋白调节的机制，其中二聚化、运动性和脂质结合由钙调蛋白调节。虽然肌球蛋白-XXI二聚体可能起到非运动性肌动蛋白交联剂的作用，但钙调素结合的单体可能在寄生虫中运输脂质货物。
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.