Proteins - continued peptide chain termination

A biological example of E° is the reduction of Fe(III) in the protein transferrin, which was introduced in Figure 7-4. This protein has two Fe(III)-binding sites, one in each half of the molecule designated C and N for the carboxyl and amino terminals of the peptide chain. Transferrin carries Fe(III) through the blood to cells that require iron. Membranes of these cells have a receptor that binds Fe(III)-transferrin and takes it into a compartment called an endosome into which H is pumped to lower the pH to —5.8. Iron is released from transferrin in the endosome and continues into the cell as Fe(II) attached to an intracellular metal-transport protein. The entire cycle of transferrin uptake, metal removal, and transferrin release back to the bloodstream takes 1-2 min. The time required for Fe(III) to dissociate from transferrin at pH 5.8 is —6 min, which is too long to account for release in the endosome. The reduction potential of Fe(IH)-transferrin at pH 5.8 is E° = —0.52 V, which is too low for physiologic reductants to reach. 

The cycle of peptide-chain elongation continues until one of the three stop codons (UAA, UAG, UGA) is reached. There is no aminoacyl-tRNA complementary to these codons, and instead a termination factor or a release factor (RF) with bound GTP binds to the ribosome and induces hydrolysis of both the aminoacyl-linkage and GTP, thereby releasing the completed polypeptide chain from the ribosome. The 475 amino acid-long sequence of rabbit liver RF has been deduced from its cDNA sequence, and it shows 90% homology with mammalian trypto-phanyl-tRNA synthetase (Lee et al., 1990). It has also been reported that for efficient and accurate termination, an additional fourth nucleotide (most commonly an A or a G) after the stop codon is required (Tate and Brown, 1992). The exact role of the fourth nucleotide in the termination of protein synthesis is not fully understood at present. 

In addition to the conventional 20 amino acids in Tables 26-1 and 26-3, two others, selenocysteine (Sec) and pyrrolysine (Pyl), are incorporated into proteins using the nueleie acid-based eell machinery described in Section 26-10. The three-base codes for Sec and Pyl are UGA and HAG, respectively. These codes normally serve to terminate protein synthesis. However, if they are preceded by certain specific base sequences, they instead cause incorporation of these unusual amino adds and continued growth of the peptide chain. 

The long, repetitive sequence of —N—CH-CO- atoms that make up a continuous chain is called the protein s backbone. By convention, peptides are written with the N-terminal amino acid (the one with the free -NH3 1 group) on the left and the C-terminal amino acid (the one with the free -C02 group) on the right. The name of the peptide is indicated by using the abbreviations listed in Table 26.1 for each amino add. Thus, alanylserine is abbreviated Ala-Ser or A-S, and serylalanine is abbreviated Ser-Ala or S-A. Needless to say, the one-letter abbreviations are more convenient than the older three-letter abbreviations. 

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