College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875, China.
Institute of Biophysics, Hebei University of Technology, Tianjin 300401, China.
Arch Biochem Biophys. 2014 Feb 1;543:10-4. doi: 10.1016/j.abb.2013.12.017. Epub 2013 Dec 27.
Conventional kinesin's force generation process always takes place on the leading head and the generated force is transmitted to the trailing head through two neck linkers. To guarantee a strong force to be transmitted to the trailing head so that it can be detached from microtubule surface, the neck linker of the leading head must have a large enough forward displacement, which is proposed to be achieved by the amplifying function of the β-domain. However, the experimental result shows that the forward displacement of the β-domain itself appears too small. To elucidate the function of the β-domain, we make a detailed analysis of the mechanical relationship between the two motor heads and, based on the results of molecular dynamics simulation and mechanical analysis, we calculate the forward displacement of the neck linker of the leading head during the ATP binding induced motor head rotation. We show that β-domain achieves its amplifying function together with β0, so that neck linker can have a forward displacement during motor head rotation. This displacement of neck linker is large enough to cause detachment of the trailing head. Based on these results, a possible initiation mechanism of neck linker docking is proposed.
传统的驱动蛋白的力产生过程总是发生在领先的头部，并且产生的力通过两个颈部接头传递到尾部头部。为了保证一个强大的力被传递到尾部头部，使其能够从微管表面脱离，领先头部的颈部接头必须有足够大的向前位移，这被提议通过β结构域的放大功能来实现。然而，实验结果表明，β结构域本身的向前位移显得太小。为了阐明β结构域的功能，我们对两个马达头部之间的力学关系进行了详细分析，并基于分子动力学模拟和力学分析的结果，计算了在 ATP 结合诱导马达头部旋转过程中领先头部颈部接头的向前位移。我们表明，β结构域与β0一起实现了其放大功能，从而使颈部接头在马达头部旋转过程中能够产生向前位移。颈部接头的这种位移足以导致尾部头部的脱离。基于这些结果，提出了一种颈部接头对接的可能起始机制。
