Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, USA.
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, USA.
Curr Biol. 2021 May 24;31(10):R560-R573. doi: 10.1016/j.cub.2021.02.035.
Microtubules are dynamic cytoskeletal filaments composed of αβ-tubulin heterodimers. Historically, the dynamics of single tubulin interactions at the growing microtubule tip have been inferred from steady-state growth kinetics. However, recent advances in the production of recombinant tubulin and in high-resolution optical and cryo-electron microscopies have opened new windows into understanding the impacts of specific intermolecular interactions during growth. The microtubule lattice is held together by lateral and longitudinal tubulin-tubulin interactions, and these interactions are in turn regulated by the GTP hydrolysis state of the tubulin heterodimer. Furthermore, tubulin can exist in either an extended or a compacted state in the lattice. Growing evidence has led to the suggestion that binding of microtubule-associated proteins (MAPs) or motors can induce changes in tubulin conformation and that this information can be communicated through the microtubule lattice. Progress in understanding how dynamic tubulin-tubulin interactions control dynamic instability has benefitted from visualizing structures of growing microtubule plus ends and through stochastic biochemical models constrained by experimental data. Here, we review recent insights into the molecular basis of microtubule growth and discuss how MAPs and regulatory proteins alter tubulin-tubulin interactions to exert their effects on microtubule growth and stability.
微管是由αβ-微管蛋白异二聚体组成的动态细胞骨架丝。从历史上看，从稳态生长动力学推断出在生长的微管尖端处的单个微管蛋白相互作用的动力学。然而，最近在重组微管蛋白的生产以及高分辨率光学和冷冻电子显微镜方面的进展为理解生长过程中特定分子间相互作用的影响开辟了新的窗口。微管晶格由横向和纵向的微管蛋白-微管蛋白相互作用保持在一起，这些相互作用反过来又受到微管蛋白异二聚体的 GTP 水解状态的调节。此外，微管蛋白在晶格中可以处于扩展或压缩状态。越来越多的证据表明，微管相关蛋白 (MAP) 或马达的结合可以诱导微管蛋白构象的变化，并且该信息可以通过微管晶格进行传递。对动态微管蛋白-微管蛋白相互作用如何控制动态不稳定性的理解的进展得益于可视化生长微管末端的结构以及通过受实验数据约束的随机生化模型。在这里，我们回顾了最近对微管生长分子基础的见解，并讨论了 MAP 和调节蛋白如何改变微管蛋白-微管蛋白相互作用以发挥其对微管生长和稳定性的影响。
