Protein synthesis posttranslational processing

The synthesis of virtually all bacterial polypeptides starts with N-formyl-Met (fMet). The N-terminal Met and other residues may be removed from certain proteins by posttranslational processings (see below). Two different species of tRNAs, tRNA, " (or tRNA ") and tRNA , carry the initiating Met and internal Met, respectively, in bacteria, chloroplasts, and mitochondria. Eukaryotic cells also contain two distinct tRNA having respective functions in initiation and elongation however, the Met on the eukaryotic initiator tRNA is not formylated. 

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.]... 

In chapter 29, Protein Synthesis, Targeting, and Turnover, the processes of protein synthesis and transport are described. First the process whereby amino acids are ordered and polymerized into polypeptide chains is described. Next, posttranslational alterations of newly synthesized polypeptides is considered. This is followed by a discussion of the targeting processes whereby proteins migrate from their site of synthesis to their target sites of function. Finally, proteolytic reactions that result in the return of proteins to their starting materials, the amino acids, are considered. 

Fig. 11.4 Mechanism of clotting factor localization to an activated platelet surface. Left After synthesis in the liver, certain blood clotting proteins are posttranslationally modified in the endoplasmic reticulum by a vitamin K-dependent Vit K carboxylase. This enzyme forms carboxyglutamate residues (top center) that chelate calcium ions. Right In the bloodstream, clotting factor-bound calcium ions attach to negatively charged phosphatidylserine that appears on the surface of activated platelets. Certain therapeutic drugs or acquired deficiencies inhibit this process - see text (Original figure submitted by Dr Paul DeAngelis, Department of Biochemistry, University of Oklahoma HSC, Oklahoma City, OK, USA)...

DNA has a form of double helix and contains nearly 3 billion base pairs, each of which consists of one of four types of nucleotides such as adenine, thymine, cytosine, and guanine. The human genome, the complete human DNA, would be equivalent to about 250 volumes of Manhattan phone directories when it is printed. Figure B.l illustrates the processes associated with protein synthesis transcription, translation, posttranslation modification (PTM), and folding. 

Protein synthesis is an extraordinarily complex process in which genetic information encoded in the nucleic acids is translated into the 20 amino acid alphabet of polypeptides. In addition to translation (the mechanism by which a nucleotide base sequence directs the polymerization of amino acids), protein synthesis can also be considered to include the processes of posttranslational modification and targeting. Posttranslational modification consists of chemical alterations cells use to prepare polypeptides for their functional roles. Several modifications assist in targeting, which directs newly synthesized molecules to a specific intracellular or extracellular location. 

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. 

Protein synthesis also involves a set of posttranslational modifications that prepare the molecule for its functional role, assist in folding, or target it to a specific destination. These covalent alterations include proteolytic processing, modification of certain amino acid side chains, and insertion of cofactors. 

After synthesis of a protein has been completed, a few amino acid residues in the primary sequence may be further modified in enzyme-catalyzed reactions that add a chemical group, oxidize, or otherwise modify specific amino acids in the protein. Because protein synthesis occurs by a process known as translation, these changes are called posttranslational modification. More than 100 different posttranslation-ally modified amino acid residues have been found in human proteins. These modifications change the structure of one or more specific amino acids on a protein in a way that may serve a regulatory function, target or anchor the protein in membranes, enhance a protein s association with other proteins, or target it for degradation (Fig. 6.14). 

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