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从反向易位中抽身:LepA/EF4细胞功能的综合观点

Taking a Step Back from Back-Translocation: an Integrative View of LepA/EF4's Cellular Function.

作者信息

Heller Jalyce L E, Kamalampeta Rajashekhar, Wieden Hans-Joachim

机构信息

Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada.

Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada

出版信息

Mol Cell Biol. 2017 May 31;37(12). doi: 10.1128/MCB.00653-16. Print 2017 Jun 15.

DOI:10.1128/MCB.00653-16
PMID:28320876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5452718/
Abstract

Protein synthesis, the translation of mRNA into a polypeptide facilitated by the ribosome, is assisted by a variety of protein factors, some of which are GTPases. In addition to four highly conserved and well-understood GTPases with known function, there are also a number of noncanonical GTPases that are implicated in translation but whose functions are not fully understood. LepA/EF4 is one of these noncanonical GTPases. It is highly conserved and present in bacteria, mitochondria, and chloroplasts, but its functional role in the cell remains unknown. LepA's sequence and domain arrangement are very similar to those of other translational GTPases, but it contains a unique C-terminal domain (CTD) that is likely essential to its specific function in the cell. Three main hypotheses about the function of LepA have been brought forward to date: (i) LepA is a back-translocase, (ii) LepA relieves ribosome stalling or facilitates sequestration, and (iii) LepA is involved in ribosome biogenesis. This review examines the structural and biochemical information available on bacterial LepA and discusses it on the background of the available information from higher organisms in order to broaden the view regarding LepA's functional role in the cell and how the structure of its unique CTD might be involved in facilitating this role.

摘要

蛋白质合成是指核糖体将信使核糖核酸(mRNA)翻译成多肽的过程,这一过程由多种蛋白质因子协助完成,其中一些是鸟苷三磷酸酶(GTPases)。除了四种功能已知的高度保守且已被充分了解的GTPases外,还有一些非典型GTPases也参与翻译过程,但其功能尚未完全明确。LepA/EF4就是这些非典型GTPases之一。它高度保守,存在于细菌、线粒体和叶绿体中,但其在细胞中的功能作用仍不清楚。LepA的序列和结构域排列与其他翻译GTPases非常相似,但它含有一个独特的C末端结构域(CTD),这可能对其在细胞中的特定功能至关重要。迄今为止,关于LepA功能的主要假设有三个:(i)LepA是一种反向转位酶;(ii)LepA可缓解核糖体停滞或促进隔离;(iii)LepA参与核糖体生物合成。这篇综述研究了关于细菌LepA的现有结构和生化信息,并在来自高等生物的现有信息背景下进行讨论,以拓宽对LepA在细胞中功能作用的认识,以及其独特CTD的结构可能如何参与促进这一作用。

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本文引用的文献

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Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome.保守的 GTPase LepA(延伸因子 4)在 70S 核糖体 30S 亚基的生物发生中起作用。
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):980-985. doi: 10.1073/pnas.1613665114. Epub 2017 Jan 17.
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The C-terminal Helix of Pseudomonas aeruginosa Elongation Factor Ts Tunes EF-Tu Dynamics to Modulate Nucleotide Exchange.铜绿假单胞菌延伸因子 Ts 的 C 末端螺旋调节 EF-Tu 动力学以调控核苷酸交换。
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A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest.联合冷冻电镜和分子动力学方法揭示 ErmBL 介导的翻译阻遏机制。
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Elongation factor 4 remodels the A-site tRNA on the ribosome.延伸因子4重塑核糖体上的A位点转运RNA。
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Mammalian elongation factor 4 regulates mitochondrial translation essential for spermatogenesis.哺乳动物延伸因子 4 调节线粒体翻译对精子发生至关重要。
Nat Struct Mol Biol. 2016 May;23(5):441-9. doi: 10.1038/nsmb.3206. Epub 2016 Apr 11.
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