Elongation proteins involved

In diphtheria, the organism C. diphtheriae eonfmes itself to epithelial surfaces of the nose and throat and produces a powerfiil toxin which affects the elongation factor involved in protein biosynthesis. The heart and peripheral nerves are particularly affected resulhng in myocarditis (inflammation of the myocardium) and neuritis (inflammation of a nerve). Little damage is produeed at the infective site. 

A third type of bacterial toxin, diphtheria toxin, catalyzes the ADP-ribosylation of eukaryotic elongation factor (EFTU), a type of small G protein involved in protein synthesis (Table 19-2). The functional activity of the elongation factor is inhibitedby this reaction. Finally, a botulinum toxin ADP-ribosylates and disrupts the function of the small G protein Rho, which appears to be involved in assembly and rearrangement of the actin cytoskeleton (Table 19-2). These toxins maybe involved in neuropathy (see Ch. 36) and membrane trafficking (see Ch. 9). 

Overview of reactions in protein synthesis. (aab aa2, aa3 = amino acids l, 2, 3.) Protein synthesis requires transfer RNAs for each amino acid, ribosomes, messenger RNA, and a number of dissociable protein factors in addition to ATP, GTP, and divalent cations. First the transfer RNAs become charged with amino acids, then the initiation complex is formed. Peptide synthesis does not start until the second aminoacyl tRNA becomes bound to the ribosome. Elongation reactions involve peptide bond formation, dissociation of the discharged tRNA, and translocation. The elongation process is repeated many times until the termination codon is reached. Termination is marked by the dissociation of the messenger RNA... 

This reaction is reversible when conducted in vitro, but under the conditions of pH and nicotinamide concentration that exist in the cell, it is irreversible. Thus, diphtheria toxin kills cells by irreversibly destroying the ability of EF-2 to participate in the translocation step of protein synthesis elongation. A number of other protein toxins have subsequently been found to ADP-ribosylate and inactivate cellular proteins involved in other essential cellular pathways. For example, cholera and pertussis toxins ADP-ribosylate and inactivate proteins important to cAMP metabolism. 

A further functionally diverse class is made up of the proteins involved in protein biosynthesis and membrane transport. GTPases with functions in protein biosynthesis include the elongation factors, termination factors and peptide translocation factors. These are mostly monomeric proteins with molecular weights of 40 - 50 kDa. 

Translation of a protein involves three steps initiation, elongation, and termination. It begins with the formation of the initiation complex. Subsequently, synthesis of the polypeptide occurs by a series of elongation steps that are repeated as each... 

The molecular mechanism of translation in eukaryotes is very similar to that in bacteria. The activation of amino acids and their attachment to tRNA molecules, and the steps of initiation, elongation, and termination of polypeptide chains, are essentially the same in overall terms. The small and large ribosomal subunits of bacteria and eukaryotes, although different is size and composition, are equivalent with respect to their roles in initiation and elongation of polypeptide chains. Differences lie mainly in the details of some steps, particularly initiation, and in the greater munher of accessory proteins involved in each step. 

The ribosome, the most complex multicomponent apparatus of the protein-synthesizing machinery, is made up of two unequal subparticles. In eukaryotes, there are over 70 proteins and at least three different RNA species which comprise the ribosome. An analogy with multienzyme complexes is suggested by the peptidyl transferase and translocation activities of the ribosome and by the multiple subunits comprising this complex. With so many proteins involved, it is likely that some serve structural roles while others serve either recognition functions or catalytic functions. The peptide bond formation requires the approximation at the ribosome of mRNA, aminoacyl-tRNA, and peptidyl-tRNA, along with necessary initiation, elongation, and termination factors. 

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