Mechanisms of microtubule dynamics and force generation examined with computational modeling and electron cryotomography
Mechanisms of microtubule dynamics and force generation examined with computational modeling and electron cryotomography
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DOI：
10.1038/s41467-020-17553-2
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发表时间：
2020-07-28
影响因子：
16.6
通讯作者：
McIntosh, J. Richard
中科院分区：
文献类型：
--
作者：
Gudimchuk, Nikita B.;Ulyanov, Evgeni, V;McIntosh, J. Richard
微管是动态微管蛋白聚合物，负责许多细胞过程，包括有丝分裂期间染色体的捕获和分离。与微管蛋白自组装的教科书模型相反，我们最近证明了通过将弯曲的三磷酸鸟苷微管蛋白添加到弯曲的原丝的尖端来延长微管。在这里，我们探讨这种机制的微管生长，使用布朗动力学建模和电子冷冻断层扫描。前面描述的喇叭形形状的增长微管尖端是非常一致的各种组装条件下，包括不同的微管蛋白浓度，存在或不存在的聚合催化剂或微管蛋白结合药物。模拟结果表明，在微管生长和缩短过程中，大量的力的发展需要一个高的激活能势垒在横向微管蛋白-微管蛋白的相互作用。建模提供了一种机制来解释动粒耦合到增长的微管提示下的辅助力，它预测了负载依赖性的加速微管组装，提供了一个角色的喇叭形形态的增长微管结束。
Microtubules are dynamic tubulin polymers responsible for many cellular processes, including the capture and segregation of chromosomes during mitosis. In contrast to textbook models of tubulin self-assembly, we have recently demonstrated that microtubules elongate by addition of bent guanosine triphosphate tubulin to the tips of curving protofilaments. Here we explore this mechanism of microtubule growth using Brownian dynamics modeling and electron cryotomography. The previously described flaring shapes of growing microtubule tips are remarkably consistent under various assembly conditions, including different tubulin concentrations, the presence or absence of a polymerization catalyst or tubulin-binding drugs. Simulations indicate that development of substantial forces during microtubule growth and shortening requires a high activation energy barrier in lateral tubulin-tubulin interactions. Modeling offers a mechanism to explain kinetochore coupling to growing microtubule tips under assisting force, and it predicts a load-dependent acceleration of microtubule assembly, providing a role for the flared morphology of growing microtubule ends.