Resolving kinesin stepping: one head at a time
Resolving kinesin stepping: one head at a time
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DOI：
10.26508/lsa.201900456
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发表时间：
2019-10-01
影响因子：
4.4
通讯作者：
Okten, Zeynep
中科院分区：
文献类型：
--
作者：
Stepp, Willi L.;Okten, Zeynep
众所周知，驱动蛋白在几乎所有的真核细胞中为各种长距离运输过程提供动力。因此，ATP依赖的进行性步进以及驱动蛋白活性的调节在过去几十年中一直是广泛研究的焦点。目前普遍认为驱动蛋白马达可以通过抑制“头部”的催化活性来自我调节其活性。在C末端的远端无规卷曲，被称为“尾域”，被认为是介导这种自抑制的;然而，尾对驱动蛋白的进行性步进的直接调节影响被证明是难以捕获的。在这里，我们同时跟踪两个不同的头域在驱动蛋白-2电机使用双色超分辨率显微镜（dcfIONA），并首次揭示他们的个人属性在进行性步进。我们发现，自抑制野生型构象选择性地影响一个头在异二聚体，但不是其他。我们的研究结果提供了深入的监管驱动蛋白步进，逃避实验审查到目前为止。
Kinesins are well known to power diverse long-range transport processes in virtually all eukaryotic cells. The ATP-dependent processive stepping as well as the regulation of kinesin' activity have, thus, been the focus of extensive studies over the past decades. It is widely accepted that kinesin motors can selfregulate their activity by suppressing the catalytic activity of the "heads." The distal random coil at the C terminus, termed "tail domain," is proposed to mediate this autoinhibition; however, a direct regulatory influence of the tail on the processive stepping of kinesin proved difficult to capture. Here, we simultaneously tracked the two distinct head domains in the kinesin-2 motor using dual-color super resolution microscopy (dcFIONA) and reveal for the first time their individual properties during processive stepping. We show that the autoinhibitory wild-type conformation selectively impacts one head in the heterodimer but not the other. Our results provide insights into the regulated kinesin stepping that had escaped experimental scrutiny so far.