Virus-encoded Aminoacyl-tRNA synthetases:: Structural and functional characterization of mimivirus TyrRS and MetRS

Virus-encoded Aminoacyl-tRNA synthetases:: Structural and functional characterization of mimivirus TyrRS and MetRS
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DOI:
10.1128/jvi.01107-07
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发表时间:
2007-11-01
影响因子:
5.4
通讯作者:
Claverie, Jean-Michel
Claverie, Jean-Michel
中科院分区:
医学2区
文献类型:
--
作者:
Abergel, Chantal;Rudinger-Thirion, Joelle;Claverie, Jean-Michel

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氨酰基-tRNA 合成酶对于确定遗传密码如何翻译为氨基酸以及为蛋白质合成提供底物至关重要。因此,它们在所有细胞生物体(从最复杂的寄生形式到最简化的寄生形式)中普遍保守的过程中发挥着关键作用。相比之下,除了 tRNA 等分离的成分外,即使是复杂的病毒也没有发现编码太多翻译机制。在这种背景下,拟菌病毒基因组中编码的四种氨酰基-tRNA合成酶以及全套翻译起始、延伸和终止因子的发现似乎模糊了细胞世界和病毒世界之间曾经清晰的界限。两种拟菌病毒 tRNA 合成酶的功能研究证实了 MetRS 对甲硫氨酸的特异性和 TyrRS 对酪氨酸的特异性,并且符合古细菌/真核生物 tRNA(Tyr) 的识别规则。拟菌病毒酪氨酰-tRNA合成酶与酪氨酸复合物的原子结构表现出古菌型TyrRS的典型折叠和活性位点组织。然而,病毒酶呈现出独特的二聚体构象,并且其反密码子结合位点存在显着差异。目前的工作表明拟菌病毒氨酰基-tRNA 合成酶在受感染的阿米巴原虫中起到常规翻译酶的作用。它们的系统发育分类并不表明它们是最近通过细胞宿主的水平基因转移获得的,而是支持大型DNA病毒和祖先真核生物之间复杂的进化关系。
Aminoacyl-tRNA synthetases are pivotal in determining how the genetic code is translated in amino acids and in providing the substrate for protein synthesis. As such, they fulfill a key role in a process universally conserved in all cellular organisms from their most complex to their most reduced parasitic forms. In contrast, even complex viruses were not found to encode much translation machinery, with the exception of isolated components such as tRNAs. In this context, the discovery of four aminoacyl-tRNA synthetases encoded in the genome of mimivirus together with a full set of translation initiation, elongation, and termination factors appeared to blur what was once a clear frontier between the cellular and viral world. Functional studies of two mimivirus tRNA synthetases confirmed the MetRS specificity for methionine and the TyrRS specificity for tyrosine and conformity with the identity rules for tRNA(Tyr) for archea/eukarya. The atomic structure of the mimivirus tyrosyl-tRNA synthetase in complex with tyrosinol exhibits the typical fold and active-site organization of archaeal-type TyrRS. However, the viral enzyme presents a unique dimeric conformation and significant differences in its anticodon binding site. The present work suggests that mimivirus aminoacyl-tRNA synthetases function as regular translation enzymes in infected amoebas. Their phylogenetic classification does not suggest that they have been acquired recently by horizontal gene transfer from a cellular host but rather militates in favor of an intricate evolutionary relationship between large DNA viruses and ancestral eukaryotes.