Molecular investigations into the unfoldase action of severing enzymes on microtubules
Molecular investigations into the unfoldase action of severing enzymes on microtubules
复制标题
切断酶对微管的解折叠酶作用的分子研究
DOI：
10.1002/cm.21606
复制
发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Dima, Ruxandra I.
中科院分区：
文献类型：
--
作者：
Varikoti, Rohith A.;Macke, Amanda C.;Speck, Virginia;Ross, Jennifer L.;Dima, Ruxandra I.
微管（MT）相关蛋白在细胞过程中调节MT的动态行为。MT切割酶是通过从晶格中去除亚基来使MT不稳定的相关蛋白质。切割酶如何从MT晶格中去除微管蛋白二聚体的一个模型是通过拉动微管蛋白二聚体的羧基末端尾部来展开其亚基。该模型源于切断酶是AAA+解折叠酶的事实。为了测试这一机制，我们使用粗粒分子模拟对MT亚基的羧基末端区域施加拉力。在我们的模拟中，我们使用不同的MT晶格和浓度的切断酶。我们比较我们的模拟结果与数据在体外切断检测，发现实验数据是最适合的合作去除原丝片段切断酶，这取决于切断酶的浓度和MT晶格上的位置的模型。
Microtubule (MT)‐associated proteins regulate the dynamic behavior of MTs during cellular processes. MT severing enzymes are the associated proteins which destabilize MTs by removing subunits from the lattice. One model for how severing enzymes remove tubulin dimers from the MT lattice is by unfolding its subunits through pulling on the carboxy‐terminal tails of tubulin dimers. This model stems from the fact that severing enzymes are AAA+ unfoldases. To test this mechanism, we apply pulling forces on the carboxy‐terminal regions of MT subunits using coarse grained molecular simulations. In our simulations, we used different MT lattices and concentrations of severing enzymes. We compare our simulation results with data from in vitro severing assays and find that the experimental data is best fit by a model of cooperative removal of protofilament fragments by severing enzymes, which depends on the severing enzyme concentration and placement on the MT lattice.