Recognizing the D-loop of transfer RNAs

Abstract

Mechanisms that maintain fidelity and repair mistakes are ubiquitous throughout the protein biosynthesis pathway (1). The aminoacyl tRNAs serve as critical turning points in translation, because they link the nucleic acid genetic code with the amino acid building blocks of proteins. Misacylation of tRNAs can have devastating results, affecting the very survivability of an organism. Accuracy in tRNA aminoacylation therefore is paramount to the fidelity of the genetic code. Aminoacyl tRNAs are generated typically through action of the diverse family of aminoacyl-tRNA synthetases (AARSs). One of the hallmarks of these enzymes is the exquisite specificity with which each selects and aminoacylates only its cognate tRNA(s) with only its cognate amino acid (2–5). Herculean efforts spanning nearly 25 years have produced crystal structures for 19 of the 20 AARSs (alanyl-tRNA synthetase is the last holdout). Many of these structures provide detailed molecular insight into the nature of tRNA recognition and discrimination by either providing a structure of the enzyme in complex with its cognate tRNA or suggesting a model that can be tested biochemically. Thus, a clear picture is beginning to emerge, delineating some of the common and not-so-common themes used by the AARSs to discriminate cognate from noncognate tRNAs. [There are several reviews available that describe tRNA recognition by AARSs in detail (4–7).]