Microtubule instability driven by longitudinal and lateral strain propagation
Microtubule instability driven by longitudinal and lateral strain propagation
复制标题
DOI：
10.1371/journal.pcbi.1008132
复制
发表时间：
2020-09-01
影响因子：
4.3
通讯作者：
Grubmueller, Helmut
中科院分区：
文献类型：
--
作者：
Igaev, Maxim;Grubmueller, Helmut
微管蛋白二聚体纵向和横向结合形成亚稳态微管(MTS)。MT拆解之前是由GTP水解推动的微管蛋白的微妙结构变化。这些变化使MT晶格不稳定，但它们究竟如何影响晶格能量学和应变尚不清楚。我们进行了长期的原子模拟，以询问GTP水解对微管蛋白晶格构象、横向二聚体间相互作用以及(非)局部横向协调二聚体运动的影响。模拟结果表明，大部分的水解能以纵向应变的形式储存在晶格中。虽然不会显著影响侧键的稳定性，但储存的弹性能量会导致GDP-微管蛋白的动力学受到更强的限制和关联，从而从熵上破坏MT晶格的稳定性。
Tubulin dimers associate longitudinally and laterally to form metastable microtubules (MTs). MT disassembly is preceded by subtle structural changes in tubulin fueled by GTP hydrolysis. These changes render the MT lattice unstable, but it is unclear exactly how they affect lattice energetics and strain. We performed long-time atomistic simulations to interrogate the impacts of GTP hydrolysis on tubulin lattice conformation, lateral inter-dimer interactions, and (non-)local lateral coordination of dimer motions. The simulations suggest that most of the hydrolysis energy is stored in the lattice in the form of longitudinal strain. While not significantly affecting lateral bond stability, the stored elastic energy results in more strongly confined and correlated dynamics of GDP-tubulins, thereby entropically destabilizing the MT lattice.