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位于核糖体组装核心位置的GTP酶Era。

GTPase Era at the heart of ribosome assembly.

作者信息

Gruffaz Christelle, Smirnov Alexandre

机构信息

UMR7156- Génétique Moléculaire, Génomique, Microbiologie (GMGM), University of Strasbourg, Centre National de la Recherche Scientifique (CNRS), Strasbourg, France.

University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg, France.

出版信息

Front Mol Biosci. 2023 Oct 4;10:1263433. doi: 10.3389/fmolb.2023.1263433. eCollection 2023.

Abstract

Ribosome biogenesis is a key process in all organisms. It relies on coordinated work of multiple proteins and RNAs, including an array of assembly factors. Among them, the GTPase Era stands out as an especially deeply conserved protein, critically required for the assembly of bacterial-type ribosomes from to humans. In this review, we bring together and critically analyze a wealth of phylogenetic, biochemical, structural, genetic and physiological data about this extensively studied but still insufficiently understood factor. We do so using a comparative and, wherever possible, synthetic approach, by confronting observations from diverse groups of bacteria and eukaryotic organelles (mitochondria and chloroplasts). The emerging consensus posits that Era intervenes relatively early in the small subunit biogenesis and is essential for the proper shaping of the platform which, in its turn, is a prerequisite for efficient translation. The timing of Era action on the ribosome is defined by its interactions with guanosine nucleotides [GTP, GDP, (p)ppGpp], ribosomal RNA, and likely other factors that trigger or delay its GTPase activity. As a critical nexus of the small subunit biogenesis, Era is subject to sophisticated regulatory mechanisms at the transcriptional, post-transcriptional, and post-translational levels. Failure of these mechanisms or a deficiency in Era function entail dramatic generalized consequences for the protein synthesis and far-reaching, pleiotropic effects on the organism physiology, such as the Perrault syndrome in humans.

摘要

核糖体生物合成是所有生物体中的关键过程。它依赖于多种蛋白质和RNA的协同工作,包括一系列组装因子。其中,GTP酶Era是一种特别高度保守的蛋白质,从细菌到人类,它对于细菌型核糖体的组装至关重要。在这篇综述中,我们汇集并批判性地分析了大量关于这个经过广泛研究但仍了解不足的因子的系统发育、生化、结构、遗传和生理学数据。我们采用比较的方法,并尽可能采用综合方法,通过对比来自不同细菌群体以及真核细胞器(线粒体和叶绿体)的观察结果来进行分析。新出现的共识认为,Era在小亚基生物合成过程中相对较早地发挥作用,对于平台的正确塑造至关重要,而平台的正确塑造又是高效翻译的先决条件。Era在核糖体上发挥作用的时机由其与鸟苷核苷酸[GTP、GDP、(p)ppGpp]、核糖体RNA以及可能触发或延迟其GTP酶活性的其他因子的相互作用所决定。作为小亚基生物合成的关键节点,Era在转录、转录后和翻译后水平受到复杂的调控机制的影响。这些机制的失效或Era功能的缺陷会对蛋白质合成产生严重的普遍后果,并对生物体生理产生深远的多效性影响,例如人类的佩罗综合征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dea7/10582724/0d62c025acba/fmolb-10-1263433-g001.jpg

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