Department of Physics, Lomonosov Moscow State University, Moscow, Russia.
Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
Nat Commun. 2020 Jul 28;11(1):3765. doi: 10.1038/s41467-020-17553-2.
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.
微管是由动态微管蛋白聚合而成的，负责许多细胞过程，包括有丝分裂过程中染色体的捕获和分离。与教科书上的微管蛋白自组装模型相反，我们最近的研究表明，微管通过将弯曲原纤维尖端的弯曲鸟苷三磷酸微管蛋白添加到微管上而延伸。在这里，我们使用布朗动力学建模和电子晶体断层扫描来探索这种微管生长的机制。在各种组装条件下，包括不同的微管蛋白浓度、聚合催化剂或微管结合药物的存在与否，生长中的微管尖端的先前描述的扩张形状都非常一致。模拟表明，在微管生长和缩短过程中产生的大的力的发展需要在侧向微管蛋白-微管蛋白相互作用中有一个高的激活能垒。该模型提供了一种机制，可以解释在辅助力下动粒与生长中的微管尖端的偶联，并且预测了微管组装的负载依赖性加速，为生长中的微管末端的扩张形态提供了作用。
