24 Control of the Elongation Phase of Protein Synthesis

Abstract

EUKARYOTIC ELONGATION FACTORS
Peptide-chain elongation is the programmed assembly of amino acids into a polypeptide as dictated by the sequence of bases in the mRNA. In all organisms it requires ancillary proteins termed elongation factors (see Chapter 3). These factors fall into two groups: (1) those required for the recruitment of aminoacyl-tRNAs to the ribosome and (2) those involved in the subsequent translocation event in which the ribosome moves along the mRNA. The proteins mediating these steps in the cytoplasm of eukaryotic cells are termed eEF1A1 and eEF2, respectively (Table 1). Both are GTP-binding proteins and the GTP is hydrolyzed during the events associated with the function of these proteins. Each protein thus ends up bound to GDP, in which state it is inactive and must be recycled to its GTP-bound form. For eEF2 this appears to occur spontaneously (due to rapid dissociation of the GDP), whereas for eEF1A/EF-Tu a guanine nucleotide-exchange factor (GEF) termed eEF1B is needed. Mammalian eEF1B consists of three subunits (α–γ), two of which (α and γ) have nucleotide-exchange activity, at least in vitro.

It is the regulation of these proteins, primarily the higher eukaryotic factors, with which this chapter is concerned. The structural organization of eEF1A, eEF1B, and eEF2 is summarized in Figure 1, which also indicates the location of known sites of phosphorylation in these proteins.

REGULATION OF ELONGATION
Why Regulate Elongation?
Altering the rate of elongation will alter the rate at which peptide chains are completed and thus is expected to contribute...