Integrated model of the vertebrate augmin complex.

Integrated model of the vertebrate augmin complex.
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DOI:
10.1038/s41467-023-37519-4
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发表时间:
2023-04-13
影响因子:
16.6
通讯作者:
Petry, Sabine
Petry, Sabine
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Travis, Sophie M.;Mahon, Brian P.;Huang, Wei;Ma, Meisheng;Rale, Michael J.;Kraus, Jodi;Taylor, Derek J.;Zhang, Rui;Petry, Sabine

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为了在细胞分裂期间保持基因组的完整性,染色体的准确分离是必需的。这一壮举是由基于微管的主轴完成的。为了快速和高保真地构建纺锤体,细胞利用分支微管成核,在细胞分裂过程中迅速放大微管。分支微管的成核依赖于异八聚体的增强蛋白复合体,但缺乏有关增强蛋白的结构信息阻碍了人们对它如何促进分支的理解。在这项工作中,我们结合了冷冻电子显微镜、蛋白质结构预测以及通过负染电子显微镜对融合的大标签进行可视化来确定增强蛋白结构中每个亚基的位置和方向。进化分析表明,Augmin的结构在真核生物中高度保守,并且包含一个先前未知的微管结合位点。因此,我们的发现为了解分支微管成核的机制提供了依据。有丝分裂纺锤体中的许多微管是通过微管分支形成的。在这里,作者报告了一个增强蛋白复合体的结构模型,并对其在微管分支中的作用进行了深入的研究。
Accurate segregation of chromosomes is required to maintain genome integrity during cell division. This feat is accomplished by the microtubule-based spindle. To build a spindle rapidly and with high fidelity, cells take advantage of branching microtubule nucleation, which rapidly amplifies microtubules during cell division. Branching microtubule nucleation relies on the hetero-octameric augmin complex, but lack of structure information about augmin has hindered understanding how it promotes branching. In this work, we combine cryo-electron microscopy, protein structural prediction, and visualization of fused bulky tags via negative stain electron microscopy to identify the location and orientation of each subunit within the augmin structure. Evolutionary analysis shows that augmin’s structure is highly conserved across eukaryotes, and that augmin contains a previously unidentified microtubule binding site. Thus, our findings provide insight into the mechanism of branching microtubule nucleation. Many microtubules in the mitotic spindle are made through microtubule branching. Here, the authors report a structural model of the augmin complex and insights into its role in microtubule branching.
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