Protein synthesis translation termination

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.]... 

Codons are composed of three nucleotide bases usually presented in Ihe mRNA language of A, G, C, and U. They are always written 5 —>3. Of the 64 possible three-base combinations, 61 code for the twenty common amino acids and three signal termination of protein synthesis (translation). Altering the nucleotide sequence in a codon can cause sient mutations (the altered codon also codes for the original amino acid), missense mutations (the altered codon codes for a different amino acid), or nonsense mutations (the altered codon is a termination... 

Unlike translational initiation, elongation, and aminoacyl tRNA synthesis, translational termination is a spontaneous process that does not require the input of energy (GTP hydrolysis). There are three codons on the mRNA that will trigger the end of translation when they appear at the A site on the ribosome UAA, UGA, and UAG. As the ribosome encounters these codons, one of two release factor proteins will bind at the A site and hy-... 

Fig. 12.4 Outline of the process of protein synthesis (translation of messenger RNA) in bacterial cells. The four stages of synthesis are shown initiation, elongation, translocation and termination with the sites of action of antibiotics. AUG is the start codon on messenger RNA (mRNA) specifying the first amino acid in bacterial proteins, N-formylmethionine. UAG, UAA and UGA are termination codons specifying no amino acid. 30S and 50S are the subunits of the ribosome. Other protein factors involved in protein synthesis are initiation factors (IF-1,2,3), elongation factors (EF-Tu and EF-G) and release factors (RF-1,2,3).

The process of protein synthesis is called translation. The genetic code words on the mRNA are decoded by tRNA. Each tRNA has an anticodon that is complementary to a codon on the mRNA. In addition the tRNA is covalently linked to its correct amino acid. Thus hydrogen bonding between codon and anticodon brings the correct amino acid to the site of protein synthesis. Translation also occurs in three stages called initiation, chain elongation, and termination. 

Protein synthesis (translation) proceeds from the N-terminal end to the C-terminal end by reading the bases along the mRNA strand in the 5 3 direction. 

In normal cells, the GDP/GTP-binding proteins, after protein synthesis, move to the cell membrane to which they become hooked by a hydrophobic farnesyl group. The y-subunit is anchored in the membrane by a post-translational modification of the C-terminal CAAX sequence (C - cystein, AA - aliphatic amino acids, X - methionine). This protein is first enzymatically farnesylated by a specific farnesyltransferase, then the AAX part is cleaved by specific proteases and finally the cystein residue is converted to a methyl ester. 

Figure 10 Alteration of the genetic code for incorporation of non-natural amino acids, (a) In nonsense suppression, the stop codon UAG is decoded by a non-natural tRNA with the anticodon CUA. In vivo decoding of the UAG codon by this tRNA is in competition with termination of protein synthesis by release factor 1 (RFl). Purified in vitro translation systems allow omission of RF1 from the reaction mixture, (b) A new codon-anticodon pair can be created using four-base codons such as GGGU. Crystal structures of these codon-anticodon complexes in the ribosomal decoding center revealed that the C in the third anticodon position interacts with both the third and fourth codon position (purple line) while the extra A in the anticodon loop does not contact the codon.(c) Non-natural base pairs also allow creation of new codon-anticodon pairs. Shown here is the interaction of the base Y with either base X or (hydrogen bonds are indicated by red dashes).

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 each stage in protein synthesis on the ribosome—-initiation, elongation, and termination—a different set of protein factors is engaged by the ribosome. Why do such protein factors, which are crucial to the translation, exist separate from the ribosome Why must they cycle on and... 

CODON Three contiguous nucleotides in mRNA that specify the amino acid to be inserted at a specific position in a polypeptide during translation of the 64 possible codons that are formed by the four types of nucleotides in SNA (nucleotides of adenine, guanine, cytosine, and uracil), 61 specify an amino acid and three (nonsense codons) specify no amino acid, but rather serve as termination signals in protein synthesis. 

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