Carter N J, Cross R A
Molecular Motors Group, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK.
Nature. 2005 May 19;435(7040):308-12. doi: 10.1038/nature03528.
Kinesin is a molecular walking machine that organizes cells by hauling packets of components directionally along microtubules. The physical mechanism that impels directional stepping is uncertain. We show here that, under very high backward loads, the intrinsic directional bias in kinesin stepping can be reversed such that the motor walks sustainedly backwards in a previously undescribed mode of ATP-dependent backward processivity. We find that both forward and backward 8-nm steps occur on the microsecond timescale and that both occur without mechanical substeps on this timescale. The data suggest an underlying mechanism in which, once ATP has bound to the microtubule-attached head, the other head undergoes a diffusional search for its next site, the outcome of which can be biased by an applied load.
驱动蛋白是一种分子行走机器，它通过沿着微管定向拖运成包的组分来组织细胞。推动定向步移的物理机制尚不清楚。我们在此表明，在非常高的向后负载下，驱动蛋白步移中的固有定向偏差可以被逆转，使得马达以一种先前未描述的依赖于ATP的向后持续性模式持续向后行走。我们发现，向前和向后的8纳米步移都发生在微秒时间尺度上，并且在这个时间尺度上两者都没有机械亚步。数据表明了一种潜在机制，即一旦ATP与附着在微管上的头部结合，另一个头部就会进行扩散搜索以寻找其下一个位点，施加的负载可能会使搜索结果产生偏差。
