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Fixing mistakes

Nature Structural Biology volume 7, pages 447–448 (2000)Cite this article

The tRNA synthetase enzymes facilitate the attachment of particular amino acids to specific tRNAs in a two-part reaction. First, they activate the amino acid via condensation with ATP (forming an aminoacyl adenylate intermediate) and second, they transfer the amino acid moiety to a cognate tRNA that contains the anticodon specific for that amino acid. These enzymes must perform their tasks well or risk insertion of the wrong amino acids into growing polypeptide chains. The fidelity of protein synthesis is maintained in part because each tRNA synthetase primarily binds only its cognate amino acid. Nevertheless, errors do sometimes occur: a similarly shaped but incorrect amino acid (such as valine instead of isoleucine) can get transferred to a tRNA molecule. Luckily, some tRNA synthetases can fix these infrequent mistakes. This proofreading ability — known as post-transfer editing — was discovered ∼30 years ago.

Isoleucyl tRNA synthetase cannot discriminate sufficiently between valine and isoleucine — it can bind and activate both of these amino acids. In 1966, Baldwin and Berg1 showed that the enzyme compensates for this poor initial discrimination with an additional proofreading step: in the presence of tRNAIle, the valyladenylate complex breaks down. They discovered that this reaction depends on an intact tRNAIle acceptor region (the site on the tRNA where the amino acid becomes attached). This suggested the possibility that valine was, in fact, being transferred to the tRNAIle, and that the enzyme was then catalyzing the hydrolysis of the valine–tRNAIle bond to release free valine and tRNAIle. However, this model was difficult to test because at the time it was not possible to make large quantities of tRNAIle charged with valine, the incorrect amino acid.

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  1. Tracy Smith
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Smith, T. Fixing mistakes. Nat Struct Mol Biol 7, 447–448 (2000). https://doi.org/10.1038/75838

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