Phospholipid-dependent regulation of the motor activity of myosin X
Phospholipid-dependent regulation of the motor activity of myosin X
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DOI：
10.1038/nsmb.2065
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发表时间：
2011-07-01
影响因子：
16.8
通讯作者：
Ikebe, Mitsuo
中科院分区：
文献类型：
--
作者：
Umeki, Nobuhisa;Jung, Hyun Suk;Ikebe, Mitsuo
肌球蛋白X参与肌动蛋白细胞骨架的重组和丝状伪足的突出。在这里，我们研究的分子机制，其中牛肌球蛋白X的调节。球状尾域以非Ca（2+）依赖的方式抑制肌球蛋白X的运动活性。结构分析表明，肌球蛋白X是单体和带4.1-ezrin-radixin-moesin（FERM）和pleckstrin同源（PH）域结合到头部分子内，形成抑制构象。磷脂酰肌醇-3，4，5-三磷酸（PtdIns（3，4，5）P（3））与PH结构域的结合逆转了尾诱导的抑制并诱导肌球蛋白X二聚体的形成。因此，PtdIns（3，4，5）P（3）结合的破坏减弱了肌球蛋白X向细胞丝状伪足顶端的移位。我们提出以下机制：首先，尾部通过分子内的头-尾相互作用抑制肌球蛋白X的运动活性，形成折叠构象;其次，磷脂结合逆转了抑制作用，破坏了折叠构象，诱导二聚体形成，从而激活了肌球蛋白X的机械和货物转运活性。
Myosin X is involved in the reorganization of the actin cytoskeleton and protrusion of filopodia. Here we studied the molecular mechanism by which bovine myosin X is regulated. The globular tail domain inhibited the motor activity of myosin X in a Ca(2+)-independent manner. Structural analysis revealed that myosin X is monomeric and that the band 4.1-ezrin-radixin-moesin (FERM) and pleckstrin homology (PH) domains bind to the head intramolecularly, forming an inhibited conformation. Binding of phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P(3)) to the PH domain reversed the tail-induced inhibition and induced the formation of myosin X dimers. Consistently, disruption of the binding of PtdIns(3,4,5)P(3) attenuated the translocation of myosin X to filopodial tips in cells. We propose the following mechanism: first, the tail inhibits the motor activity of myosin X by intramolecular head-tail interactions to form the folded conformation; second, phospholipid binding reverses the inhibition and disrupts the folded conformation, which induces dimer formation, thereby activating the mechanical and cargo transporter activity of myosin X.