Protein synthesis polypeptide chain

To form a globular protein, a polypeptide chain must repeatedly fold back on itself. The turns or bends by which this is accomplished can be regarded as a third major secondary structural element in proteins. Turns often have precise structures, a few of which are illustrated in Fig. 2-24. As components of the loops of polypeptide chains in active sites, turns have a special importance for the functioning of enzymes and other proteins. In addition, tight turns are often sites for modification of proteins after their initial synthesis (Section F). 

What can be accomplished by protein turnover One benefit is the removal of proteins that have sustained spontaneous hydrolytic damage or oxidative damage. Another benefit is that protein turnover makes possible the control of enzyme levels by means of genetic regulation. In a condition where an increase in the acbvity of a parbcular enzyme is needed, the rale of transcripbon of the mRNA coding for the enzyme can be increased. This increase results in an increase in translation, that is, the synthesis of the protein s polypeptide chain. In a condition... 

The ER signal peptide is 10 amino acids long, is present on the NH2 terminus of ER-targeted proteins, and consists of mostly hydrophobic residues. Nascent polypeptide chains on polyribosomes that contain the ER signal peptide are directed to the ER membrane to complete protein synthesis polypeptides lacking this signal peptide are... 

Messenger RNA, formed by structural genes (segments of DNA) is the active template for synthesis of protein molecules (polypeptide chains). This RNA is complementary in the sequence of its nucleotides to particular genetic segments of one of the polynucleotides of DNA, and because of this it receives (transcribes) its information. This information is later translated in a special biochemical system of decoding into the form of a definite amino acid sequence. 

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

Transfer RNA (tRNA) serves as a carrier of amino acid residues for protein synthesis. Transfer RNA molecules also fold into a characteristic secondary structure (marginal figure). The amino acid is attached as an aminoacyl ester to the 3 -terminus of the tRNA. Aminoacyl-tRNAs are the substrates for protein biosynthesis. The tRNAs are the smallest RNAs (size range—23 to 30 kD) and contain 73 to 94 residues, a substantial number of which are methylated or otherwise unusually modified. Transfer RNA derives its name from its role as the carrier of amino acids during the process of protein synthesis (see Chapters 32 and 33). Each of the 20 amino acids of proteins has at least one unique tRNA species dedicated to chauffeuring its delivery to ribosomes for insertion into growing polypeptide chains, and some amino acids are served by several tRNAs. For example, five different tRNAs act in the transfer of leucine into... 

ATP synthase actually consists of two principal complexes. The spheres observed in electron micrographs make up the Fj unit, which catalyzes ATP synthesis. These Fj spheres are attached to an integral membrane protein aggregate called the Fq unit. Fj consists of five polypeptide chains named a, j3, y, 8, and e, with a subunit stoichiometry ajjSaySe (Table 21.3). Fq consists of three hydrophobic subunits denoted by a, b, and c, with an apparent stoichiometry of ajbgCg.ig- Fq forms the transmembrane pore or channel through which protons move to drive ATP synthesis. The a, j3, y, 8, and e subunits of Fj contain 510, 482, 272, 146, and 50 amino acids, respectively, with a total molecular mass... 

The a-amino group of the new aminoacyl-tRNA in the A site carries out a nucleophilic attack on the esterified carboxyl group of the peptidyl-tRNA occupying the P site (peptidyl or polypeptide site). At initiation, this site is occupied by aminoacyl-tRNA mef. This reaction is catalyzed by a peptidyltransferase, a component of the 285 RNA of the 605 ribosomal subunit. This is another example of ribozyme activity and indicates an important—and previously unsuspected—direct role for RNA in protein synthesis (Table 38-3). Because the amino acid on the aminoacyl-tRNA is already activated, no further energy source is required for this reaction. The reaction results in attachment of the growing peptide chain to the tRNA in the A site. 

Successive amino acids are joined together during protein synthesis via a peptide (i.e. amide) bond (Figure 2.2). This is a condensation reaction, as a water molecule is eliminated during bond formation. Each amino acid in the resultant polypeptide is termed a residue , and the polypeptide chain will display a free amino (NH2) group at one end and a free carboxyl (COOH) group at the other end. These are termed the amino and carboxyl termini respectively. 

It has long been known that peptides of bacterial origin, such as N-formylat-ed oligopeptides, are potent activators of neutrophils. Bacterial protein biosynthesis is initiated by the codon AUG, which codes for polypeptide chains at the NH2 terminus to start with N-formylmethionine. However, very few mature bacterial proteins actually have this amino acid at the NH2 terminus because Af-formylmethionine is cleaved off by proteolytic processing. Sometimes just this amino acid is cleaved, but often several adjacent residues are also removed with it. These observations formed the basis for the chemical synthesis of a variety of N-formylated oligopeptides and an assessment of their ability to activate neutrophils in vitro. The most potent of these formylated peptides is TV-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). 

The hydrophobic peptide segments of El and E2, which attach the spike protein to the lipid bilayer, can be localized on the polypeptide chains by a mapping procedure first used by Dintzis (1961) to show that the synthesis of polypeptide chains begins at the amino-terminal end. The hydrophobic stubs left in the viral membrane after protease treatment are found at the carboxyl-terminal ends of both the El and the E2 polypeptides (Garoff and Sdderlund, 1978). 

Figure 13.3 The process of protein synthesis on the ribosome. The strand of mRNA is shown associated with the small subunit of the ribosome. The aminoacyl-tRNA molecules are shown associated with the large subunit of the ribosome and base-paired with mRNA codons. A peptide bond is in the process of formation between the two associated amino acids, extending the growing polypeptide chain by one unit. On the left, a tRNA is shown leaving the ribosome, having donated its amino acid to the growing chain. On the right, an aminoacyl-tRNA molecule is shown entering the ribosome. It is next in line to contribute its amino acid to that chain.

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