Eukaryotes, protein synthesis initiation

Lamphear, B. J., Kirchweger, R., Skem, T., and Rhoads, R. E. (1995). Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. J. Biol. Chem. 270, 21975—21983. 

The binding of interferons to their receptors induces a rapid increase in the transcription of particular genes and synthesis of corresponding proteins.196 202 One of the proteins induced is a double-stranded RNA-activated 2 -5 A synthase, which polymerizes ATP to a series of 2 -5 linked oligonucleotides containing triphosphates at the 5 termini.202-204 Double-stranded RNA is uncommon except in replicating viruses, and it is thought that the activation by dsRNA is related to establishment of an antiviral state. Another interferon-induced enzyme is the small subunit of eukaryotic protein synthesis initiation factor eIF-2. 

M. Bushell, W. Wood, M.J. Clemens, and S.J. Morley. 2000. Changes in integrity and association of eukaryotic protein synthesis initiation factors during apoptosis Eur. J. Biochem. 267 1083-1091. (PubMed)... 

Roles of Eukaryotic Initiation Factor 2 Ancillary Factors in the Regulation of Eukaryotic Protein Synthesis Initiation Naba K. Gupta... 

Konieczny, A., and Safer, B. (1983). Purification of the eukaryotic initiation factor 2-eukaryotic initiation factor 2B complex and characterization of its guanine nucleotide exchange activity during protein synthesis initiation. J. Biol. Chem. 258, 3402—3408. 

An understanding of protein synthesis, the most complex biosynthetic process, has been one of the greatest challenges in biochemistry. Eukaryotic protein synthesis involves more than 70 different ribosomal proteins 20 or more enzymes to activate the amino acid precursors a dozen or more auxiliary enzymes and other protein factors for the initiation, elongation, and termination of polypeptides perhaps 100 additional enzymes for the final processing of different proteins and 40 or more kinds of transfer and ribosomal RNAs. Overall, almost 300 different macromolecules cooperate to synthesize polypeptides. Many of these macromolecules are organized into the complex three-dimensional structure of the ribosome. 

The pathway of protein synthesis translates the three-letter alphabet of nucleotide sequences on mRNA into the twenty-letter alphabet of amino acids that constitute proteins. The mRNA is translated from its 5 -end to its 3 -end, producing a protein synthesized from its amino-terminal end to its carboxyl-terminal end. Prokaryotic mRNAs often have several coding regions, that is, they are polycistronic (see p. 420). Each coding region has its own initiation codon and produces a separate species of polypeptide. In contrast, each eukaryotic mRNA codes for only one polypeptide chain, that is, it is monocistronic. The process of translation is divided into three separate steps initiation, elongation, and termination. The polypeptide chains produced may be modified by posttranslational modification. Eukaryotic protein synthesis resembles that of prokaryotes in most details. [Note Individual differences are mentioned in the text.]... 

Figure 29-11 Initiation of eukaryotic protein synthesis. 1, 2, 3 = elFl S...

Rhoads RE. Regulation of eukaryotic protein synthesis by initiation factors. J Biol Chem 268 3017-3020, 1993. 

High concentrations of hemin inhibit the transport of ALA synthase into the mitochondria, where one of the substrates, succinyl-CoA, is formed. Thus, heme synthesis is inhibited until enough globin is made to react with any heme already formed. Low concentrations, or the absence, of hemin is the signal that globin is not needed this protein (and, therefore, globin) synthesis is inhibited. In the absence of hemin, a protein kinase is activated this phosphorylates an initiation factor of (eukaryotic) protein synthesis, eIF-2, which then inhibits polypeptide chain initiation (Chap. 17) and hence inhibits globin synthesis. 

Eukaryotic Protein Synthesis Differs from Prokaryotic Protein Synthesis Primarily in Translation Initiation... 

T.V. Pestova and C.U. Hellen. 2000. The structure and function of initiation factors in eukaryotic protein synthesis Cell Mol. Life Sci. 57 651-674. (PubMed)... 

Eukaryotic protein synthesis is slower and more complex than its prokaryotic counterpart. In addition to requiring a larger number of translation factors and a more complex initiation mechanism, the eukaryotic process also involves vastly more complicated posttranslational processing and targeting mechanisms. Eukaryotes use a wide spectrum of translational control mechanisms. 

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. 

Fig. 15.9. Bacterial tRNA containing formyl-methionine. The initial methionine is not formylated in eukaryotic protein synthesis.

The Control of the Rate of Initiation of Eukaryotic Protein Synthesis... 

The mechanism of protein synthesis in eukaryotic cells is also essentially the same as in bacteria. However, since eukaryotic protein synthesis occurs in the cytoplasm, the processes of transcription and translation are not as closely coupled as they are in bacteria. In eukaryotes the initiating methionine is not formylated, but is attached to a different form of tRNA from that involved in incorporating internal methionine residues. 

Kaempfer, R., Hollender, R., Abrams, W. R., and Israeli, R., 1978a, Specific binding of messenger RNA and methionyl-tRNAf by the same initiation factor for eukaryotic protein synthesis, Proc. Natl. Acad. Sci. USA 75 209. 

Schreier, M. H., and Staehelin, T., 1973, Initiation of eukaryotic protein synthesis (Met-tRNAf.40 S ribosome) initiation complex catalysed by purified initiation factors in the absence of mRNA, Nature New Biol. 242 35. 

CuNDLiFFE, E., and J. E. Davies Inhibition of initiation, elongation and termination of eukaryotic protein synthesis by trichothecene fungal toxins. Antimicrob. Agents Chemother. 11, 491 (1977). 

The Control of the Rate of Initiation of Eukaryotic Protein Synthesis H. O. Voorma, H. Goumans, H. Amesz, and R. Benne... 

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