Eukaryotic peptide elongation

Eukaryotic peptide elongation follows similar processes as prokaryotes via aminoacyl-tRNA binding, transpeptidation and translocation, involving the A, P and E sites of the ribosome. Two elongation factors, EFl and EF2 mediate the elongation steps. EFl consists of two components, EFl A equivalent of EF-Tu and EFIB equivalent of EF-Ts. EF2 is the translocation factor that binds GTP and catalyzes hydrolysis of GTP that accompanies translocation. 

Eukaryotic peptide chain elongation factor-2 Triosephosphate isomerase Myo-inositol-phosphate synthase Mannose-1-phosphate guanylj transferase Alcohol dehydrogenase Aldehyde reductase Ade5... 

Bears a structural resemblance to aminoacyl-tRNA and becomes incorporated into the growing peptide chain, thus causing inhibition of further elongation in both prokaryotea and eukaryotes. 

Once the initiating fMet-tRNA of bacteria or the eukaryotic Met-tRNA is in place in the P site of a ribosome and is paired with the initiation codon in the mRNA, peptide chain growth can commence. Amino acid residues are added in turn by insertion at the C-terminal end of the growing peptide chain. Elongation requires three processes repeated over and over until the entire peptide is formed. 

At the conclusion of the initiation process, the ribosome is poised to translate the reading frame associated with the initiator codon. The translation of the contiguous codons in mRNA is accomplished by the sequential repetition of three reactions with each amino acid. These three reactions of elongation are similar in both prokaryotic and eukaryotic systems two of them require nonribosomal proteins known as elongation factors (EF). Interestingly, the actual formation of the peptide bond does not require a factor and is the only reaction of protein synthesis catalyzed by the ribosome itself. 

Be able to describe the mechanism for peptide chain initiation, elongation, and termination in prokaryotes and eukaryotes on the ribosome. 

The correctly positioned eukaryotic SOS ribosome-Met-tRNAj complex is now ready to begin the task of stepwise addition of amino acids by the in-frame translation of the mRNA. As is the case with initiation, a set of special proteins, termed elongation factors (EFs), are required to carry out this process of chain elongation. The key steps in elongation are entry of each succeeding aminoacyl-tRNA, formation of a peptide bond, and the movement, or translocation, of the ribosome one codon at a time along the mRNA. 

Following peptide bond synthesis, the ribosome Is translocated along the mRNA a distance equal to one codon. This translocation step is promoted by hydrolysis of the GTP in eukaryotic EF2-GTP. As a result of translocation, tRNAj , now without its activated methionine, is moved to the E (exit) site on the ribosome concurrently, the second tRNA, now covalently bound to a dIpeptIde (a peptIdyl-tRNA), Is moved to the P site (Figure 4-26, step U). Translocation thus returns the ribosome conformation to a state in which the A site Is open and able to accept another amlnoacylated tRNA complexed with EFlct-GTP, beginning another cycle of chain elongation. 

Peptide chain elongation in eukaryotes is very similar to that of prokaryotes. The same mechanism of peptidyl transferase and ribosome translocation is seen. The structure of the eukaryotic ribosome is different in that there is no E site, only the A and P sites. There are two eukaryotic elongation factors, eEFl and eEF2. The eEFl consists of two subunits, eEFlA and eEFlB. The 1A subunit is the counterpart of EF-Tu in prokaryotes. The IB subunit is the equivalent of the EF-Ts in prokaryotes. The eEF2 protein is the counterpart of the prokaryotic EF-G, which causes translocation. 

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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