Structure of the microtubule-anchoring factor NEDD1 bound to the γ-tubulin ring complex.

IF 7.4 1区 生物学 Q1 CELL BIOLOGY
Journal of Cell Biology Pub Date : 2025-08-04 Epub Date: 2025-05-21 DOI:10.1083/jcb.202410206
Hugo Muñoz-Hernández, Yixin Xu, Aitor Pellicer Camardiel, Daniel Zhang, Allen Xue, Amol Aher, Ellie Walker, Florina Marxer, Tarun M Kapoor, Michal Wieczorek
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引用次数: 0

Abstract

The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule-organizing centers (MTOCs) by the evolutionarily conserved attachment factor NEDD1. However, the structural basis of the NEDD1-γ-TuRC interaction is not known. Here, we report cryo-EM structures of NEDD1 bound to the human γ-TuRC in the absence or presence of the activating factor CDK5RAP2. We found that the C-terminus of NEDD1 forms a tetrameric α-helical assembly that contacts the lumen of the γ-TuRC cone and orients its microtubule-binding domain away from the complex. The structure of the γ-TuRC simultaneously bound to NEDD1 and CDK5RAP2 reveals that both factors can associate with the "open" conformation of the complex. Our results show that NEDD1 does not induce substantial conformational changes in the γ-TuRC but suggest that anchoring of γ-TuRC-capped microtubules by NEDD1 would be structurally compatible with the significant conformational changes experienced by the γ-TuRC during microtubule nucleation.

结合γ-微管蛋白环复合物的微管锚定因子NEDD1的结构。
γ-微管蛋白环复合物(γ-TuRC)是一种重要的多蛋白组装体,为微管成核提供了模板。γ-TuRC通过进化保守的附着因子NEDD1招募到微管组织中心(MTOCs)。然而,NEDD1-γ-TuRC相互作用的结构基础尚不清楚。在这里,我们报告了在缺乏或存在活化因子CDK5RAP2的情况下,NEDD1与人γ-TuRC结合的低温电镜结构。我们发现NEDD1的c端形成了一个四聚体α-螺旋组装体,它与γ-TuRC锥体的腔体接触,并使其微管结合域远离配合物。同时结合NEDD1和CDK5RAP2的γ-TuRC的结构表明,这两个因子都可以与复合物的“开放”构象相关联。我们的研究结果表明,NEDD1不会引起γ-TuRC的明显构象变化,但表明NEDD1对γ-TuRC帽微管的锚定与微管成核过程中γ-TuRC发生的显著构象变化在结构上是相容的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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