Protein synthesis initiation process

In this section, we describe the three basic stages of protein synthesis initiation, elongation, and termination. These three processes are fairly similar between prokaryotes and eukaryotes, with the two exceptions being that more protein factors have been identified as necessary for eukaryotic protein synthesis, and that transcription and translation are physically linked in prokaryotes but not in eukaryotes. Note that the reactions will be schematized as a single ribosome transversing the mRNA, but as shown in Figure 26.3, translation actually occurs on polyribosomes. 

To this point, you have become familiar with the molecules that participate in protein synthesis and the genetic code, the language that directs the synthesis. We now investigate the actual process by which polypeptide chains are assembled. There are three major stages in protein synthesis initiation of the polypeptide chain, elongation of the chain, and termination of the completed polypeptide chain. 

Samuel, C. E., 1979, Mechanism of interferon action Phosphorylation of protein synthesis initiation factor eIF-2 in interferon treated human cells by a ribosome associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase, Proc. Natl Acad. Sci. USA 76 600. 

Cation control of equilibrium and rate processes in initiation of protein synthesis. M. Grunberg-Manago, H. B. Hoa, P. Douzou and A. Wishnia, Adv. Inorg. Biochem., 1981, 3,193-232 (78). 

Initiation of protein synthesis requires that an mRNA molecule be selected for translation by a ribosome. Once the mRNA binds to the ribosome, the latter finds the correct reading frame on the mRNA, and translation begins. This process involves tRNA, rRNA, mRNA, and at least ten eukaryotic initiation factors (elFs), some of which have multiple (three to eight) subunits. Also involved are GTP, ATP, and amino acids. Initiation can be divided into four steps (1) dissociation of the ribosome into its 40S and 60S subunits (2) binding of a ternary complex consisting of met-tRNAf GTP, and eIF-2 to the 40S ribosome to form a preinitiation complex (3) binding of mRNA to the 40S preinitiation complex to form a 43S initiation complex and (4) combination of the 43S initiation complex with the 60S ribosomal subunit to form the SOS initiation complex. 

Figure 38-6. Diagrammatic representation of the initiation of protein synthesis on the mRNA template containing a 5 cap (G" TP-5 ) and 3 poiy(A) terminai [3 (A)J. This process proceeds in three steps (1) activation of mRNA ...

IFl-3). In contrast, eukaryotic initiation is a rather complex process involving a large number of initiation factors (elFs, Table 1). This is also the stage of eukaryotic ribosomal protein synthesis, which is most highly regulated to achieve differential protein expression. Elaborating the details of eukaryotic initiation is beyond the scope of this chapter. 

Interferons—a family of glycoproteins processed by macrophages—also are widely used as immunostimulants (a -interferons), made in macrophages and fibroblasts (j3-interferons), made in lymphocytes (7-interferons), which are named for their ability to react with viral RNA and affect protein synthesis. Commercially accessible a-, fi-, and y-interferons are currently used in medicine. Practically the only purely synthetic immunos-timulant drug that is used is levamisole, which was initially proposed as an anthelminthic agent, and it is currently widely used as such. 

The translation of the mRNA into proteins is the final step in the biological flow of information (see Fig. 6.1). Similar to other macromolecular polymerizations, protein synthesis can be divided into initiation, chain elongation, and termination. Critical players in this process are the aminoacyl transfer RNAs (tRNAs). These molecules form the interface between the mRNA and the growing polypeptide. Activation of tRNA involves the addition of an amino acid to its acceptor stem, a reaction catalyzed by an aminoacyl-tRNA synthetase. Each aminoacyl-tRNA synthetase is highly specific for one amino acid and its corresponding tRNA molecule. The anticodon loop of each aminoacyl-tRNA interacts... 

At one point or another during protein synthesis, several other proteins will be associated with the ribosome. These include factors that help in initiating the synthetic process, others that help in elongating the peptide chain, and yet others that play a role in terminating the synthesis of a peptide chain. Beyond this, there is also the mRNA to consider, as well as the aminoacylated tRNA molecules. Finally, since protein biosynthesis consumes energy, there is the hydrolysis of ATP and GTP to AMP and GDP, respectively, by the ribosome. 

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