Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA.
Structure. 2012 Apr 4;20(4):628-40. doi: 10.1016/j.str.2012.02.013. Epub 2012 Apr 3.
Kinesin walks processively on microtubules in an asymmetric hand-over-hand manner with each step spanning 16 nm. We used molecular simulations to determine the fraction of a single step due to conformational changes in the neck linker, and that due to diffusion of the tethered head. Stepping is determined largely by two energy scales, one favoring neck-linker docking and the other, ε(h)(MT-TH), between the trailing head (TH) and the microtubule. Neck-linker docking and an optimal value of ε(h)(MT-TH) are needed to minimize the probability that the TH takes side steps. There are three major stages in the kinematics of a step. In the first, the neck linker docks, resulting in ∼(5-6) nm movements of the trailing head. The TH moves an additional (6-8) nm in stage II by anisotropic translational diffusion. In the third stage, spanning ∼(3-4) nm, the step is complete with the TH binding to the αβ-tubulin binding site.
驱动蛋白以不对称的协同方式在微管上进行逐步运动，每步跨越 16nm。我们使用分子模拟来确定单个步骤中由于颈部接头的构象变化和连接头部扩散而导致的部分。步幅主要由两个能量尺度决定，一个有利于颈部接头对接，另一个是尾部头部（TH）与微管之间的 ε(h)(MT-TH)。需要颈部接头对接和 ε(h)(MT-TH) 的最佳值，以最小化尾部头部发生侧步的概率。在一个步幅的运动学中有三个主要阶段。在第一阶段，颈部接头对接，导致尾部头部移动约 5-6nm。在第二阶段，TH 通过各向异性的平移扩散再移动 6-8nm。在第三阶段，跨度约 3-4nm，TH 与 αβ-微管结合位点结合，完成了步幅。
