Distinct domains of tRNA synthetase recognize the same base pair
Distinct domains of tRNA synthetase recognize the same base pair
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DOI：
10.1038/nature06454
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发表时间：
2008-01-03
期刊：
影响因子：
64.8
通讯作者：
Schimmel, Paul
中科院分区：
文献类型：
--
作者：
Beebe, Kirk;Mock, Marissa;Schimmel, Paul
氨酰转移RNA合成酶通过其同源tRNA的精确氨酰化和其通过编辑反应纠正氨酰化的偶然错误的能力来防止含有错误（误译）的蛋白质的合成（1-5）。误译的一个主要来源是将甘氨酸或丝氨酸误认为丙氨酸，这可能导致严重的细胞和动物病理学，包括神经变性（3）。一个特定的GNU碱基对（G3中心点U 70）标志着一个tRNA被丙氨酰-tRNA合成酶氨酰化（6-9）。当甘氨酸或丝氨酸连接到含有G3中心点U 70的tRNA时，就会发生错误翻译，并通过清除错误氨基酸的编辑活性来防止。以前，人们认为识别tRNA（Ala）进行编辑的特异性是由与氨酰化相同的结构决定簇提供的。在这里，我们表明，作为人工重组片段的丙氨酰-tRNA合成酶的编辑位点，使用与氨酰化无关的结构基序靶向带错电荷的tRNA（Ala），因此，值得注意的是，同一酶中的两个基序（一个用于氨酰化，一个用于编辑）可以独立地提供tRNA（Ala）识别的决定簇。用于编辑的结构基序也天然存在于基因组编码的蛋白质片段中，其在进化中广泛分布（10-12）。这些也识别错误的tRNA（Ala）。因此，通过进化，具有相同tRNA的三种不同复合物可以防止将甘氨酸或丝氨酸误认为丙氨酸。
Synthesis of proteins containing errors ( mistranslation) is prevented by aminoacyl transfer RNA synthetases through their accurate aminoacylation of cognate tRNAs and their ability to correct occasional errors of aminoacylation by editing reactions(1-5). A principal source of mistranslation comes from mistaking glycine or serine for alanine, which can lead to serious cell and animal pathologies, including neurodegeneration(3). A single specific GNU base pair ( G3 center dot U70) marks a tRNA for aminoacylation by alanyl-tRNA synthetase(6-9). Mistranslation occurs when glycine or serine is joined to the G3 center dot U70- containing tRNAs, and is prevented by the editing activity that clears the mischarged amino acid. Previously it was assumed that the specificity for recognition of tRNA(Ala) for editing was provided by the same structural determinants as used for aminoacylation. Here we show that the editing site of alanyl-tRNA synthetase, as an artificial recombinant fragment, targets mischarged tRNA(Ala) using a structural motif unrelated to that for aminoacylation so that, remarkably, two motifs ( one for aminoacylation and one for editing) in the same enzyme independently can provide determinants for tRNA(Ala) recognition. The structural motif for editing is also found naturally in genome-encoded protein fragments that are widely distributed in evolution(10-12). These also recognize mischarged tRNA(Ala). Thus, through evolution, three different complexes with the same tRNA can guard against mistaking glycine or serine for alanine.