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Modular assembly of the nucleolar pre-60S ribosomal subunit

机译：核仁60S前核糖体亚基的模块组装。

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摘要

Early co-transcriptional events during eukaryotic ribosome assembly result in the formation of precursors of the small (40S) and large (60S) ribosomal subunits1. A multitude of transient assembly factors regulate and chaperone the systematic folding of pre-ribosomal RNA subdomains. However, owing to a lack of structural information, the role of these factors during early nucleolar 60S assembly is not fully understood. Here we report cryo-electron microscopy (cryo-EM) reconstructions of the nucleolar pre-60S ribosomal subunit in different conformational states at resolutions of up to 3.4 angstrom. These reconstructions reveal how steric hindrance and molecular mimicry are used to prevent both premature folding states and binding of later factors. This is accomplished by the concerted activity of 21 ribosome assembly factors that stabilize and remodel pre-ribosomal RNA and ribosomal proteins. Among these factors, three Brix-domain proteins and their binding partners form a ring-like structure at ribosomal RNA (rRNA) domain boundaries to support the architecture of the maturing particle. The existence of mutually exclusive conformations of these pre-60S particles suggests that the formation of the polypeptide exit tunnel is achieved through different folding pathways during subsequent stages of ribosome assembly. These structures rationalize previous genetic and biochemical data and highlight the mechanisms that drive eukaryotic ribosome assembly in a unidirectional manner.
机译：真核生物核糖体组装过程中的早期共转录事件导致小（40S）和大（60S）核糖体亚基的前体形成。大量的瞬时装配因子调节并陪伴了核糖体前RNA亚结构域的系统折叠。然而，由于缺乏结构信息，这些因素在核仁60S早期组装过程中的作用尚不完全清楚。在这里，我们报告了在不同构象状态下核仁前60S核糖体亚基的冷冻电子显微镜（cryo-EM）重建，分辨率高达3.4埃。这些重建揭示了如何使用位阻和分子模拟来防止过早的折叠状态和后继因子的结合。这是通过稳定和重塑核糖体前RNA和核糖体蛋白的21种核糖体装配因子的协同活性来实现的。在这些因素中，三个糖度域蛋白及其结合伴侣在核糖体RNA（rRNA）域边界处形成环状结构，以支持成熟粒子的结构。这些前60S粒子相互排斥的构象的存在表明，在核糖体组装的后续阶段中，多肽出口通道的形成是通过不同的折叠途径实现的。这些结构使以前的遗传和生化数据合理化，并突出了以单向方式驱动真核生物核糖体装配的机制。

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  • 来源
    《Nature》 |2018年第7699期|126-129|共4页
  • 作者

    Sanghai Zahra Assur; Miller Linamarie; Molloy Kelly R.; Barandun Jonas; Hunziker Mirjam; Chaker-Margot Malik; Wang Junjie; Chait Brian T.; Klinge Sebastian;

  • 作者单位

    Rockefeller Univ, Lab Prot & Nucle Acid Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Prot & Nucle Acid Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Prot & Nucle Acid Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Prot & Nucle Acid Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Prot & Nucle Acid Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10065 USA;

    Rockefeller Univ, Lab Prot & Nucle Acid Chem, New York, NY 10065 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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