Effects of α-tubulin acetylation on microtubule structure and stability
Effects of α-tubulin acetylation on microtubule structure and stability
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DOI：
10.1073/pnas.1900441116
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发表时间：
2019-05-21
影响因子：
11.1
通讯作者：
Nogales, Eva
中科院分区：
文献类型：
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作者：
Eshun-Wilson, Lisa;Zhang, Rui;Nogales, Eva
微管蛋白中K40的乙酰化是标记微管管腔表面的唯一翻译后修饰。它与微管稳定的关系是相关的还是因果的，目前还存在争议。我们获得了α - tat1乙酰化和sirt2去乙酰化微管纯样品的高分辨率低温电子显微镜（cro - em）重建，以可视化这种修饰的结构后果，并揭示其影响微管更大组装特性的潜力。我们利用实验低温电镜密度作为分子动力学模拟中的结构约束，模拟了未修饰态和乙酰化态的构象群。我们发现乙酰化改变了包含α K40的柔性环的构象景观。对K40的修改减少了环路的无序性，限制了其采样的状态。我们提出，我们所描述的构象采样的变化，在非常接近侧接触部位的位置，可能会影响微管的稳定性和功能。
Acetylation of K40 in alpha-tubulin is the sole posttranslational modification to mark the luminal surface of microtubules. It is still controversial whether its relationship with microtubule stabilization is correlative or causative. We have obtained high-resolution cryo-electron microscopy (cryo-EM) reconstructions of pure samples of alpha TAT1-acetylated and SIRT2-deacetylated microtubules to visualize the structural consequences of this modification and reveal its potential for influencing the larger assembly properties of microtubules. We modeled the conformational ensembles of the unmodified and acetylated states by using the experimental cryo-EM density as a structural restraint in molecular dynamics simulations. We found that acetylation alters the conformational landscape of the flexible loop that contains alpha K40. Modification of alpha K40 reduces the disorder of the loop and restricts the states that it samples. We propose that the change in conformational sampling that we describe, at a location very close to the lateral contacts site, is likely to affect microtubule stability and function.