4 A Comparative View of Initiation Site Selection Mechanisms

Abstract

Initiation can be defined as the process in which a special initiator tRNA, formyl-Met-tRNA_f or Met-tRNA_i, is positioned in the P site of a ribosome located at the correct AUG codon (or in some cases a non-AUG initiation codon). When the initiation stage is complete, the ribosome is capable of dipeptide formation if it is presented with nothing more than a ternary complex of EF1A (formerly EF-Tu), GTP, and the cognate aminoacyl-tRNA appropriate for the A-site codon. A detailed description of the pathway of events involved in initiation in both prokaryotes and eukaryotes is provided in Chapter 2.

What is quite remarkable is that in prokaryotic systems this process of initiation requires just three initiation factor proteins, each of them a single polypeptide chain and with an aggregate mass of 150 kD, in contrast to at least ten separate initiation factors in eukaryotes, totaling over 25 polypeptide chains with an aggregate size approaching 1200 kD. Given this remarkable difference, it doesn’t require exceptional imagination to come up with the suggestion that something is fundamentally different between initiation in the two systems! (Note that throughout this chapter, the term “prokaryotic” will be taken to imply eubacterial, specifically Escherichia coli, and “eukaryotic” to signify cytoplasmic mRNA translation in eukaryotes. No attempt will be made to cover mRNA translation in Archaebacteria or in eukaryotic organelles.)

It is tempting to speculate that this disparity in the complexity of initiation factors is mainly due to differences in the mechanism of initiation site selection, which is...