Precision of Protein Biosynthesis

Abstract

INTRODUCTION
In translation, the cyclic selection of amino acids to become associated with cognate tRNAs, and of aminoacyl-tRNAs (aa-tRNAs) to donate their amino acids to the growing peptide chain, must be carried out rapidly to yield a biologically functional protein product. Despite these demanding requirements, the fraction of the product that is accurately formed—the “yield,” in chemical jargon—is probably greater than 90%. Later in this paper we discuss the value of this number in more detail. This extraordinary performance has attracted much experimentation, which was forseen in the pioneering studies of Luigi Gorini.

For brevity and concreteness, we have concentrated on the accuracy of coding; i.e., the accuracy with which aa-tRNAs are matched to codons. We further confine discussion to chain extension. On related topics, there is an excellent recent review of chain initiation (Gold et al. 1981). Similarly, there are other recent sources of information about the accuracy of synthesis of aa-tRNAs (Yarus 1979a), and two independent and roughly contemporary surveys of translational accuracy can be compared with this one (see Buckingham and Grosjean 1983; Kurland and Gallant 1983). A survey of the earlier literature, and a different point of view, may be found in the text of Yarus (1979b). Finally, the reader desiring the broad view should not forget that translational error is always seen against a background of transcriptional errors (Rosenberger and Foskett 1981), still largely uncharacterized.

ACCURACY AND KINETICS
Accuracy is a matter of the relative rates of reaction of two similar substrates (e.g....