Crystal structure of the mitotic spindle kinesin Eg5 reveals a novel conformation of the neck-linker
Crystal structure of the mitotic spindle kinesin Eg5 reveals a novel conformation of the neck-linker
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DOI：
10.1074/jbc.m100395200
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发表时间：
2001-07-06
影响因子：
4.8
通讯作者：
Sakowicz, R
中科院分区：
文献类型：
--
作者：
Turner, J;Anderson, R;Sakowicz, R
有丝分裂的成功取决于许多细胞因子的协调和调节活性，包括驱动蛋白马达蛋白，其是有丝分裂纺锤体的组装和功能所需的。Eg 5是一种与双极纺锤体的形成及其在分裂后期之前和期间的运动有关的驱动蛋白。我们已经确定了与ADP-Mg结合的Eg 5马达结构域的晶体结构。这一结构揭示了一个新的分子内结合位点的颈连接。在其他驱动蛋白中，颈连接体已被证明是力产生的关键机械元件。传统驱动蛋白的颈连接体在沿着微管移位时被认为经历有序到无序的转变。Eg 5的结构显示了一个有序的颈连接体构象的位置从来没有观察到以前。颈接头的对接依赖于仅在驱动蛋白马达的Eg 5亚家族中保守的残基。基于这一新的信息，我们认为，颈部连接Eg 5可能会经历一个有序的有序过渡过程中生产力。这种棘轮样机制与Eg 5的生物活性一致。
Success of mitosis depends upon the coordinated and regulated activity of many cellular factors, including kinesin motor proteins, which are required for the assembly and function of the mitotic spindle. Eg5 is a kinesin implicated in the formation of the bipolar spindle and its movement prior to and during anaphase. We have determined the crystal structure of the Eg5 motor domain with ADP-Mg bound. This structure revealed a new intramolecular binding site of the neck-linker. In other kinesins, the neck-linker has been shown to be a critical mechanical element for force generation. The neck-linker of conventional kinesin is believed to undergo an ordered-to-disordered transition as it translocates along a microtubule. The structure of Eg5 showed an ordered neck-linker conformation in a position never observed previously. The docking of the neck-linker relies upon residues conserved only in the Eg5 subfamily of kinesin motors. Based on this new information, we suggest that the neck-linker of Eg5 may undergo an ordered-to-ordered transition during force production. This ratchet-like mechanism is consistent with the biological activity of Eg5.