The CC1-FHA Tandem as a Central Hub for Controlling the Dimerization and Activation of Kinesin-3 KIF1A
The CC1-FHA Tandem as a Central Hub for Controlling the Dimerization and Activation of Kinesin-3 KIF1A
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CC1-FHA 串联作为控制驱动蛋白 3 KIF1A 二聚化和激活的中心枢纽
DOI：
10.1016/j.str.2012.07.002
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发表时间：
2012-09-05
期刊：
影响因子：
5.7
通讯作者：
Feng, Wei
中科院分区：
文献类型：
--
作者：
Huo, Lin;Yue, Yang;Feng, Wei
Kinesin-3 KIF1A 在轴突运输和突触发生中发挥着重要作用。 KIF1A 在体外采用单体形式，但在体内作为持续二聚体发挥作用。运动二聚化的机制尚不清楚。在这里，我们发现 KIF1A 的 CC1-FHA 串联体以稳定的二聚体形式存在。 CC1-FHA的结构揭示了CC1和FHA之间的连接子意外地形成了β-指发夹，其将CC1与FHA整合，组装CC1-FHA同二聚体。更重要的是，CC1-FHA 二聚体的解离释放了 CC1 和 β 指，这两者对于运动抑制都是必需的。因此，CC1-FHA 串联的二聚化不仅促进 KIF1A 二聚体的形成，而且还可能通过隔离 CC1/β 指区域来触发运动活动。 CC1-FHA 串联可能充当控制 KIF1A 二聚化和激活的中枢，这可能代表了其他驱动蛋白-3 马达共享的驱动蛋白调节的新范例。
Kinesin-3 KIF1A plays prominent roles in axonal transport and synaptogenesis. KIF1A adopts a monomeric form in vitro but acts as a processive dimer in vivo. The mechanism underlying the motor dimerization is poorly understood. Here, we find that the CC1-FHA tandem of KIF1A exists as a stable dimer. The structure of CC1-FHA reveals that the linker between CC1 and FHA unexpectedly forms a beta-finger hairpin, which integrates CC1 with FHA assembling a CC1-FHA homodimer. More importantly, dissociation of the CC1-FHA dimer unleashes CC1 and the beta-finger, which are both essential for the motor inhibition. Thus, dimerization of the CC1-FHA tandem not only promotes the KIF1A dimer formation but also may trigger the motor activity via sequestering the CC1/beta-finger region. The CC1-FHA tandem likely functions as a hub for controlling the dimerization and activation of KIF1A, which may represent a new paradigm for the kinesin regulation shared by other kinesin-3 motors.