Predicting the pathway involved in post-translational modification of elongation factor P in a subset of bacterial species.
Predicting the pathway involved in post-translational modification of elongation factor P in a subset of bacterial species.
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DOI：
10.1186/1745-6150-5-3
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发表时间：
2010-01-13
期刊：
影响因子：
5.5
通讯作者：
de Crécy-Lagard V
中科院分区：
文献类型：
--
作者：
Bailly M;de Crécy-Lagard V
细菌延伸因子 P (EF-P) 在细菌中严格保守，对于蛋白质合成至关重要。它与真核翻译起始因子 5A (eIF5A) 同源。高度保守的 eIF5A 赖氨酸被修饰成源自亚精胺的不寻常氨基酸，即马尿氨酸。 Hypusine 对于 eIF5A 在酿酒酵母翻译中的作用是绝对必需的。 EF-P的同源赖氨酸在大肠杆菌中也被修饰为亚精胺衍生物。然而，细菌 EF-P 中这种修饰的生物合成途径尚未阐明。在这里，我们提出了 EF-P 翻译后修饰的潜在机制。通过使用基于物理聚类和系统发育模式分析的比较基因组方法，我们鉴定了由大肠杆菌中的 yjeA 和 yjeK 基因编码的两个功能未知的蛋白质家族，作为该缺失途径的候选者。基于对两个蛋白质家族的结构和生化特性的分析，我们提出了 EF-P 修饰的两种潜在机制。这个假设可以通过构建带有标记的 efp 基因的细菌菌株来进行基因测试。该标签允许通过亲和层析纯化 EF-P，并通过质谱分析纯化的蛋白质。然后可以在 efp 标记的菌株中删除 yjeA 或 yjeK，并通过质谱法分析从每个突变体中纯化的 EF-P 蛋白是否存在修饰。这一假设也可以通过纯化不同的成分（YjeK、YjeA 和 EF-P）并在体外重建途径来检验。某些细菌中蛋白质合成需要完全修饰的 EF-P，这意味着这些生物体中存在特定的翻译后修饰机制。分析的所有 725 个细菌基因组都具有 efp 基因，但只有 200 个（28%）同时具有 yjeA 和 yjeK 基因。在其他生物体中，EF-P 可能被其他途径修饰，或者翻译机器必须适应 EF-P 修饰的缺乏。我们的假设如果得到证实，将导致新的翻译后修饰途径的发现。本文由 Céline Brochier-Armanet、Igor B. Zhulin 和 Mikhail Gelfand 审阅。如需完整评论，请访问审稿人报告部分。
The bacterial elongation factor P (EF-P) is strictly conserved in bacteria and essential for protein synthesis. It is homologous to the eukaryotic translation initiation factor 5A (eIF5A). A highly conserved eIF5A lysine is modified into an unusual amino acid derived from spermidine, hypusine. Hypusine is absolutely required for eIF5A's role in translation in Saccharomyces cerevisiae. The homologous lysine of EF-P is also modified to a spermidine derivative in Escherichia coli. However, the biosynthesis pathway of this modification in the bacterial EF-P is yet to be elucidated. Here we propose a potential mechanism for the post-translational modification of EF-P. By using comparative genomic methods based on physical clustering and phylogenetic pattern analysis, we identified two protein families of unknown function, encoded by yjeA and yjeK genes in E. coli, as candidates for this missing pathway. Based on the analysis of the structural and biochemical properties of both protein families, we propose two potential mechanisms for the modification of EF-P. This hypothesis could be tested genetically by constructing a bacterial strain with a tagged efp gene. The tag would allow the purification of EF-P by affinity chromatography and the analysis of the purified protein by mass spectrometry. yjeA or yjeK could then be deleted in the efp tagged strain and the EF-P protein purified from each mutant analyzed by mass spectrometry for the presence or the absence of the modification. This hypothesis can also be tested by purifying the different components (YjeK, YjeA and EF-P) and reconstituting the pathway in vitro. The requirement for a fully modified EF-P for protein synthesis in certain bacteria implies the presence of specific post-translational modification mechanism in these organisms. All of the 725 bacterial genomes analyzed, possess an efp gene but only 200 (28%) possess both yjeA and yjeK genes. In the other organisms, EF-P may be modified by another pathway or the translation machinery must have adapted to the lack of EF-P modification. Our hypotheses, if confirmed, will lead to the discovery of a new post-translational modification pathway. This article was reviewed by Céline Brochier-Armanet, Igor B. Zhulin and Mikhail Gelfand. For the full reviews, please go to the Reviewers' reports section.
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