Myosin X dimerization and its impact on cellular functions.
Myosin X dimerization and its impact on cellular functions.
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肌球蛋白 X 二聚化及其对细胞功能的影响。
DOI：
10.1073/pnas.1216035109
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发表时间：
2012
影响因子：
11.1
通讯作者：
Yengo,ChristopherM
中科院分区：
文献类型：
--
作者：
Quintero,OmarA;Yengo,ChristopherM
肌动蛋白分子马达肌球蛋白超家族的所有成员都被认为利用ATP水解产生的能量来产生力和运动。一些肌球蛋白能够通过位于马达催化区（头部）C末端的卷曲螺旋结构域形成平行卷曲螺旋二聚体（1）。这种形式的二聚化被认为是肌球蛋白（作为细胞内转运蛋白）的双手交替进行性行走机制所必需的（2）。在这种行走机制中，马达的机械化学性质使得二聚体的至少一个头部附着在肌动蛋白丝上的可能性很高，这是由于步长与肌动蛋白丝的螺距紧密匹配以及应变门控机制，其中两个头部的酶循环是协调的（2）。进行性行走允许多个连续的步骤和长距离运输沿着一个单一的肌动蛋白丝。在PNAS上发表的一项研究中，Lu et al. (3)证明了肌球蛋白X（MYO 10）的反平行二聚化机制，并表明这种结构安排允许更有效的进行性行走在丝状伪足的平行肌动蛋白束。此外，Lu et al. (3)证明反平行卷曲螺旋的形成增强了MYO 10诱导丝状伪足形成的能力，一个高度争论的话题是不同类型的肌球蛋白如何在不同的肌动蛋白结构中发挥作用（例如，平行束，反平行束，和分支/交联网络）以及是否存在有效运动所需的肌球蛋白的特定结构域和/或或者说在这些肌动蛋白结构中产生力。最近，Brawley和Rock（4）的工作表明，当MYO 5、MYO 6或MYO 10的单个分子暴露于Triton提取的多种细胞类型的细胞骨架时，每种肌球蛋白的“交通”模式都不同，这表明不同肌动蛋白网络结构的运动特异性。Lu等人提出，反平行二聚化对于MYO 10以“跨骑样”方式行走可能是重要的，除了以更类似于肌动蛋白的方式行走之外，每个头部与肌动蛋白束内的相邻肌动蛋白丝相关。
All members of the myosin su-perfamily of actin-based molecular motors are thought to use the energy from ATP hydrolysis to generate force and motion. Some myosins are capable of forming parallel coiled-coil dimers by virtue of a coiled-coil domain that is C-terminal to the motor catalytic region (head)(1). This form of dimerization is thought to be essential for the hand-over-hand processive walking mechanism of myosins that function as intracellular transporters (2). In this walking mechanism the mechanochemical properties of the motors are such that the likelihood of at least one head of the dimer being attached to the actin filament is high, owing to a step size that closely matches the helical pitch of the actin filament and a strain-gating mechanism in which the enzymatic cycles of the two heads are coordinated (2). Processive walking allows for multiple successive steps and long-distance transport along a single actin filament. In a study presented in PNAS, Lu et al.(3) demonstrate an antiparallel dimerization mechanism in myosin X (MYO10) and suggest that this structural arrangement allows more efficient processive walking in the parallel actin bundles of filopodia. In addition, Lu et al.(3) demonstrate that formation of the antiparallel coiled coil enhances the ability of MYO10 to induce filopodia formation.A highly debated topic has been how different classes of myosin function within the diverse actin-based structures (eg, parallel bundles, antiparallel bundles, and branched/cross-linked networks) that exist in cells and whether there are specific domains of myosin required for efficient movement and/or force generation in these actin-based structures. Recently, work by Brawley and Rock (4) demonstrated that when single molecules of MYO5, MYO6, or MYO10 were exposed to Triton-extracted cytoskeletons of a number of cell types, the patterns of “traffic” for each myosin were different, suggesting motor specificity for different actin network architectures. Lu et al. propose that the antiparallel dimerization may be important for MYO10 to walk in a “straddle-like” fashion, with each head associated with an adjacent actin filament within the actin bundles, in addition to walking in a manner more similar to the