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研究揭示核孔的细胞质表面结构
作者:小柯机器人 发布时间:2022/6/12 23:35:50

美国加州理工学院André Hoelz研究团队揭示核孔的细胞质表面结构。相关论文于2022年6月10日发表在《科学》杂志上。

研究人员报告了人类核孔复合体(NPC)细胞质面的复合结构,该结构是通过结合生化重组、晶体结构测定、对接低温电子断层成像重建和生理学验证获得的。而物种特异性的模体将演化保守的~540千卡的异六聚体细胞质丝核孔蛋白复合物固定在中央运输通道之上,NUP358五聚体束的附着取决于外套核孔蛋白复合物的双环排列。这个复合物结构及其预测能力为阐明mRNA输出和核蛋白疾病的分子基础提供了丰富的基础。
 
据介绍,NPC是核细胞质运输的唯一双向通道。尽管最近在阐明NPC对称核心结构方面取得了进展,但对mRNA输出至关重要的不对称装饰的细胞质面,以及核孔蛋白相关疾病的一个热点,仍然难以捉摸。
 
附:英文原文

Title: Architecture of the cytoplasmic face of the nuclear pore

Author: Christopher J. Bley, Si Nie, George W. Mobbs, Stefan Petrovic, Anna T. Gres, Xiaoyu Liu, Somnath Mukherjee, Sho Harvey, Ferdinand M. Huber, Daniel H. Lin, Bonnie Brown, Aaron W. Tang, Emily J. Rundlet, Ana R. Correia, Shane Chen, Saroj G. Regmi, Taylor A. Stevens, Claudia A. Jette, Mary Dasso, Alina Patke, Alexander F. Palazzo, Anthony A. Kossiakoff, André Hoelz

Issue&Volume: 2022-06-10

Abstract: The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating the NPC symmetric core architecture, the asymmetrically decorated cytoplasmic face, essential for messenger RNA (mRNA) export and a hotspot for nucleoporin-associated diseases, has remained elusive. Here we report a composite structure of the human cytoplasmic face obtained by combining biochemical reconstitution, crystal structure determination, docking into cryo–electron tomographic reconstructions, and physiological validation. Whereas species-specific motifs anchor an evolutionarily conserved ~540-kilodalton heterohexameric cytoplasmic filament nucleoporin complex above the central transport channel, attachment of the NUP358 pentameric bundles depends on the double-ring arrangement of the coat nucleoporin complex. Our composite structure and its predictive power provide a rich foundation for elucidating the molecular basis of mRNA export and nucleoporin diseases.

DOI: abm9129

Source: https://www.science.org/doi/10.1126/science.abm9129

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037