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研究揭示微管聚集因子γ-TuRC的组装与激活过程
2019-12-24 15:42

2019年12月19日,《自然》在线发表了德国海德堡大学的Elmar Schiebel、Stefan Pfeffer等研究人员的一项最新研究成果。研究解析了微管(MT)聚集因子γ-TuRC的组装与激活过程。

研究人员表示,MT是αβ-微管蛋白的动态聚合物,在细胞信号传导、细胞迁移、胞内转运过程和染色体分离中起关键作用。通过称为MT聚集的基本过程从α/β-微管蛋白二聚体重新组装。包含蛋白质γ-微管蛋白的复合物可作为MT聚集反应的结构模板。在脊椎动物中,MT由大小为2.2 MDa的γ-微管蛋白环复合物(γ-TuRC)形成聚集,该复合物由γ-微管蛋白、五个相关的γ-微管蛋白复合蛋白(GCP2-6)和其他因子组成。GCP6在GCP家族蛋白中是唯一的,因为它带有未知功能的扩展插入域。无法获得有关γ-TuRC的高分辨率结构信息,这严重限制了我们对细胞和组织中MT形成的理解。

研究人员报道了非洲爪蟾的γ-TuRC的冷冻电镜结构,其全局分辨率为4.8Å,从而揭示了GCP和γ-微管蛋白的14辐排列在部分柔性的开放左手螺旋中,并具有均匀的GCP变体序列。通过与其他GCP蛋白的特异性相互作用,GCP6特异性插入结构域可支撑γ-TuRC的组装。出乎意料的是,研究人员将肌动蛋白鉴定为γ-TuRC的真正结构成分,在MT聚集中具有功能相关性。γ-TuRC螺旋几何形状对于MT聚集而言不是最理想的,因此激活它需要对γ-TuRC进行受控的构象重排。总的来说,这一冷冻电镜重建为脊椎动物γ-TuRC的分子组织、组装和激活机制提供了新的见识,并将成为对与MT聚集相关的基本生物学过程(例如减数分裂和有丝分裂纺锤体的形成以及中心粒的生成)进行机械理解的重要框架。

附:英文原文

Title: Insights into the assembly and activation of the microtubule nucleator γ-TuRC

Author: Peng Liu, Erik Zupa, Annett Neuner, Anna Bhler, Justus Loerke, Dirk Flemming, Thomas Ruppert, Till Rudack, Christoph Peter, Christian Spahn, Oliver J. Gruss, Stefan Pfeffer, Elmar Schiebel

Issue&Volume: 2019-12-19

Abstract: Microtubules (MTs) are dynamic polymers of αβ-tubulin and play critical roles in cell signaling, cell migration, intracellular transport processes and chromosome segregation1. They assemble de novo from α/β-tubulin dimers in an essential process termed MT nucleation. Complexes containing the protein γ-tubulin serve as structural templates for the MT nucleation reaction2. In vertebrates, MTs are nucleated by the 2.2 MDa γ-tubulin ring complex (γ-TuRC) composed of γ-tubulin, five related γ-tubulin complex proteins (GCP2-6) and additional factors3. GCP6 is unique among the GCP proteins, because it carries an extended insertion domain of unknown function. High-resolution structural information on the γ-TuRC is not available, strongly limiting our understanding of MT formation in cells and tissue2. Here, we present the cryo-EM structure of γ-TuRC from Xenopus laevis at 4.8 global resolution, revealing a 14-spoked arrangement of GCPs and γ-tubulins in a partially flexible open left-handed spiral with a uniform sequence of GCP variants (Fig. 1a). Via specific interactions with other GCP proteins, the GCP6-specific insertion domain scaffolds the assembly of the γ-TuRC. Unexpectedly, we identified Actin as a bona fide structural component of γ-TuRC with functional relevance in MT nucleation. The γ-TuRC spiral geometry is suboptimal for MT nucleation and a controlled conformational rearrangement of the γ-TuRC is required for its activation. Collectively, our cryo-EM reconstruction provides unprecedented insights into the molecular organization, the assembly and the activation mechanism of vertebrate γ-TuRC and will serve as an important framework for the mechanistic understanding of fundamental biological processes associated with MT nucleation, e.g. meiotic and mitotic spindle formation and centriole biogensis4.

DOI: 10.1038/s41586-019-1896-6

Source: https://www.nature.com/articles/s41586-019-1896-6

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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