Varga Vladimir, Leduc Cecile, Bormuth Volker, Diez Stefan, Howard Jonathon
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Cell. 2009 Sep 18;138(6):1174-83. doi: 10.1016/j.cell.2009.07.032.
Motor proteins in the kinesin-8 family depolymerize microtubules in a length-dependent manner that may be crucial for controlling the length of organelles such as the mitotic spindle. We used single-molecule microscopy to understand the mechanism of length-dependent depolymerization by the budding yeast kinesin-8, Kip3p. We found that after binding at a random position on a microtubule and walking to the plus end, an individual Kip3p molecule pauses there until an incoming Kip3p molecule bumps it off. Kip3p dissociation is accompanied by removal of just one or two tubulin dimers (on average). Such a cooperative mechanism leads to a depolymerization rate that is proportional to the flux of motors to the microtubule end and accounts for the length dependence of depolymerization. This type of feedback between length and disassembly may serve as a model for understanding how an ensemble of molecules can measure and control polymer length.
驱动蛋白-8家族中的驱动蛋白以长度依赖的方式使微管解聚，这对于控制诸如有丝分裂纺锤体等细胞器的长度可能至关重要。我们使用单分子显微镜来了解出芽酵母驱动蛋白-8（Kip3p）的长度依赖性解聚机制。我们发现，一个Kip3p分子在微管上的随机位置结合并向正端移动后，会在那里暂停，直到一个进入的Kip3p分子将其撞落。Kip3p的解离平均仅伴随着一两个微管蛋白二聚体的去除。这种协同机制导致解聚速率与驱动蛋白向微管末端的通量成正比，并解释了解聚的长度依赖性。长度与拆卸之间的这种反馈类型可作为理解分子集合如何测量和控制聚合物长度的模型。
