小柯机器人

细胞内核孔结构获解析
2020-09-03 15:27

德国欧洲分子生物学实验室Martin Beck、Jan Kosinski和马克斯·普朗克生物化学研究所Boris Pfander团队合作,揭示了细胞内核孔结构及其转换机制。 该项研究成果在线发表在2020年9月2号的《自然》杂志上。

研究人员利用原位结构生物学和相关光学和电子显微镜整合建模,以及分子扰动结合核膜重塑的方法对完整酿酒酵母细胞的核孔复合物(NPC)进行了结构分析。研究人员发现了先前体外分析未揭示的核孔蛋白(Nups)亚复合物的原位构象和构型。Nup159复合物的构型对于其作为mRNA出核口和NPC周转介质功能都至关重要。

聚集在nup116Δ细胞中的Ω型核被膜疝部分掩盖了缺少多个亚复合体的组装NPC,包括Nup159复合体。在饥饿条件下形成了第二种核被膜疝,其导致NPC暴露于胞质。

这些结果揭示了NPC转换模型,即含有NPC的囊泡在被自噬机器降解之前从核被膜中离开。该研究突出了在细胞环境中研究大分子复合物结构-功能关系的重要性。

研究人员表示,NPC融合了核被膜的内膜和外膜。它们由数百个Nups构成并组装为多个亚复合物,这形成了用于核质交换的大中央通道。但对于这种结构如何促进信使RNA出核、NPC生物发生和核质交换仍然知之甚少。

附:英文原文

Title: In-cell architecture of the nuclear pore and snapshots of its turnover

Author: Matteo Allegretti, Christian E. Zimmerli, Vasileios Rantos, Florian Wilfling, Paolo Ronchi, Herman K. H. Fung, Chia-Wei Lee, Wim Hagen, Beata Turoov, Kai Karius, Mandy Brmel, Xiaojie Zhang, Christoph W. Mller, Yannick Schwab, Julia Mahamid, Boris Pfander, Jan Kosinski, Martin Beck

Issue&Volume: 2020-09-02

Abstract: Nuclear pore complexes (NPCs) fuse the inner and outer membranes of the nuclear envelope. They comprise hundreds of nucleoporins (Nups) that assemble into multiple subcomplexes and form large central channels for nucleocytoplasmic exchange1,2. How this architecture facilitates messenger RNA export, NPC biogenesis and turnover remains poorly understood. Here we combine in situ structural biology and integrative modelling with correlative light and electron microscopy and molecular perturbation to structurally analyse NPCs in intact Saccharomyces cerevisiae cells within the context of nuclear envelope remodelling. We find an in situ conformation and configuration of the Nup subcomplexes that was unexpected from the results of previous in vitro analyses. The configuration of the Nup159 complex appears critical to spatially accommodate its function as an mRNA export platform, and as a mediator of NPC turnover. The omega-shaped nuclear envelope herniae that accumulate in nup116Δ cells3 conceal partially assembled NPCs lacking multiple subcomplexes, including the Nup159 complex. Under conditions of starvation, herniae of a second type are formed that cytoplasmically expose NPCs. These results point to a model of NPC turnover in which NPC-containing vesicles bud off from the nuclear envelope before degradation by the autophagy machinery. Our study emphasizes the importance of investigating the structure–function relationship of macromolecular complexes in their cellular context.

DOI: 10.1038/s41586-020-2670-5

Source: https://www.nature.com/articles/s41586-020-2670-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
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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