Processivity of the single-headed kinesin KIF1A through biased binding to tubulin
Processivity of the single-headed kinesin KIF1A through biased binding to tubulin
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DOI：
10.1038/nature01804
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发表时间：
2003-07-31
期刊：
影响因子：
64.8
通讯作者：
Hirokawa, N
中科院分区：
文献类型：
--
作者：
Okada, Y;Higuchi, H;Hirokawa, N
传统的马达蛋白驱动蛋白的亚型在功能上不是作为“单分子”，而是作为“双分子”配对。这种二聚体结构构成了解决其机制的障碍（1-4）。为了克服这个问题，我们使用非传统的驱动蛋白KIF 1A（参考文献5，6）作为模型分子。KIF 1A作为一个独立的单体（7，8）移动到前体，也可以作为一个功能性二聚体（9）协同工作。在这里，我们通过用光学捕获系统（10）测量其运动，表明单个ATP水解触发单个KIF 1A单体的单个步进运动。步长随机分布在8 nm的倍数附近，具有高斯状包络和15 nm的标准偏差。平均而言，该步骤是定向的微管的正端对抗高达0.15 pN的负载力。作为这种定向运动的来源，我们发现KIF 1A在与微管结合时向微管的正端移动了大约3 nm，推测是通过优先结合微管蛋白的正端侧。我们提出了一个简单的物理公式来解释KIF 1A的运动。
Conventional isoforms of the motor protein kinesin behave functionally not as 'single molecules' but as 'two molecules' paired. This dimeric structure poses a barrier to solving its mechanism(1-4). To overcome this problem, we used an unconventional kinesin KIF1A (refs 5, 6) as a model molecule. KIF1A moves processively as an independent monomer(7,8), and can also work synergistically as a functional dimer(9). Here we show, by measuring its movement with an optical trapping system(10), that a single ATP hydrolysis triggers a single stepping movement of a single KIF1A monomer. The step size is distributed stochastically around multiples of 8 nm with a gaussian-like envelope and a standard deviation of 15 nm. On average, the step is directional to the microtubule's plus-end against a load force of up to 0.15 pN. As the source for this directional movement, we show that KIF1A moves to the microtubule's plus-end by similar to3 nm on average on binding to the microtubule, presumably by preferential binding to tubulin on the plus-end side. We propose a simple physical formulation to explain the movement of KIF1A.