Kinetic costs of accuracy in translation



In this chapter we focus attention on enzymic selections in which kinetic proofreading (Hopfield, 1974; Ninio, 1975) contributes to the accuracy. We discuss, in particular, ribosomal translation, which is the most costly (Ingraham, Maal0e and Neidhardt, 1983), as well as the noisiest step (Bouadloun, Donner and Kurland, 1983) on the path from gene to protein. In a short, historical, section we discuss the shortcomings of equilibrium thermodynamics as well as of information theory to describe enzymic selections. This discussion provides a background to the proofreading concept. It is followed by discussions on the thermodynamic flows and driving forces that are necessary for enzymic selections in general (Kurland, 1978), as well as for kinetic proofreading in particular (Blomberg, Ehrenberg and Kurland, 1980; Blomberg, 1983a, b). Our discussion about the costs of accuracy in translation starts with an experimental section where the data obtained from a set of bacterial mutants are reviewed. These measurements illustrate in a dramatic way that ‘high accuracy’ ribosomes have a reduced kinetic efficiency in vitro as well as impaired elongation rate and growth rate in vivo. These results motivate a novel analysis of the kinetic costs of accuracy in growing bacteria (Kurland and Ehrenberg, 1984; Ehrenberg and Kurland, 1984), which is contrasted with previous cost analyses based on the dissipative losses of enzymic selections (Bennet, 1979; Savageau and Freter, 1979a, b; Freter and Savageau, 1980; Blomberg, Ehrenberg and Kurland, 1980).


Peptide Bond Ternary Complex Rich Medium Elongation Rate Total Free Energy 
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