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Insights into allosteric control of microtubule dynamics from a buried β-tubulin mutation that causes faster growth and slower shrinkage.
Protein Science ( IF 4.5 ) Pub Date : 2020-02-19 , DOI: 10.1002/pro.3842
Xuecheng Ye 1 , Tae Kim 1 , Elisabeth A Geyer 1 , Luke M Rice 1
Affiliation  

αβ-tubulin subunits cycle through a series of different conformations in the polymer lattice during microtubule growing and shrinking. How these allosteric responses to different tubulin:tubulin contacts contribute to microtubule dynamics, and whether the contributions are evolutionarily conserved, remains poorly understood. Here, we sought to determine whether the microtubule-stabilizing effects (slower shrinking) of the β:T238A mutation we previously observed using yeast αβ-tubulin would generalize to mammalian microtubules. Using recombinant human microtubules as a model, we found the mutation caused slow microtubule shrinking, indicating that this effect of the mutation is indeed conserved. However, unlike in yeast, β:T238A human microtubules grew faster than wild-type and the mutation did not appear to attenuate the conformational change associated with GTP hydrolysis in the lattice. We conclude that assembly-dependent conformational change in αβ-tubulin can contribute to determine the rates of microtubule growing as well as shrinking. Our results also suggest that an allosteric perturbation like the β:T238A mutation can alter the behavior of terminal subunits without accompanying changes in the conformation of fully surrounded subunits in the body of the microtubule. This article is protected by copyright. All rights reserved.

中文翻译:

通过掩埋的β-微管蛋白突变对微管动力学的变构控制的见解,该突变导致更快的生长和更慢的收缩。

在微管生长和收缩期间,αβ-微管蛋白亚基循环通过聚合物晶格中的一系列不同构象。这些对不同微管蛋白:微管蛋白接触的变构反应如何影响微管动力学,以及这些贡献是否在进化上保守,仍知之甚少。在这里,我们试图确定我们先前使用酵母αβ-微管蛋白观察到的β:T238A突变的微管稳定作用(减缓收缩)是否会推广到哺乳动物微管。使用重组人微管作为模型,我们发现该突变引起缓慢的微管收缩,表明该突变的作用确实是保守的。但是,与酵母不同,β:T238A人类微管的生长速度快于野生型,而该突变似乎并未减弱与GTP水解相关的构象变化。我们得出结论,αβ-微管蛋白的装配依赖性构象变化可有助于确定微管的生长和收缩速率。我们的结果还表明,像β:T238A突变这样的变构扰动可以改变末端亚基的行为,而不会伴随微管体内完全包围的亚基构象的变化。本文受版权保护。版权所有。我们的结果还表明,像β:T238A突变这样的变构扰动可以改变末端亚基的行为,而不会伴随微管体内完全包围的亚基构象的变化。本文受版权保护。版权所有。我们的结果还表明,像β:T238A突变这样的变构扰动可以改变末端亚基的行为,而不会伴随微管体内完全包围的亚基构象的变化。本文受版权保护。版权所有。
更新日期:2020-02-19
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