Anticodon , interactions with codons

It has been known for some time that tetracyclines are accumulated by bacteria and prevent bacterial protein synthesis (Fig. 4). Furthermore, inhibition of protein synthesis is responsible for the bacteriostatic effect (85). Inhibition of protein synthesis results primarily from dismption of codon-anticodon interaction between tRNA and mRNA so that binding of aminoacyl-tRNA to the ribosomal acceptor (A) site is prevented (85). The precise mechanism is not understood. However, inhibition is likely to result from interaction of the tetracyclines with the 30S ribosomal subunit because these antibiotics are known to bind strongly to a single site on the 30S subunit (85). 

The information contained in the DNA (i.e., the order of the nucleotides) is first transcribed into RNA. The messenger RNA thus formed interacts with the amino-acid-charged tRNA molecules at specific cell organelles, the ribosomes. The loading of the tRNA with the necessary amino acids is carried out with the help of aminoacyl-tRNA synthetases (see Sect. 5.3.2). Each separate amino acid has its own tRNA species, i.e., there must be at least 20 different tRNA molecules in the cells. The tRNAs contain a nucleotide triplet (the anticodon), which interacts with the codon of the mRNA in a Watson-Crick manner. It is clear from the genetic code that the different amino acids have different numbers of codons thus, serine, leucine and arginine each have 6 codewords, while methionine and tryptophan are defined by only one single nucleotide triplet. 

Figure 3 Cognate and near-cognate codon-anticodon interactions. The anticodon ioop of tRNA is shown as an example interacting with various codons on the mRNA. In correct, cognate codon-anticodon pairings, two Watson-Crick base pairs can be formed in the first two positions while the third position contains either a Watson-Crick or a wobble base pair.

In incorrect, near-cognate interactions, one mismatch is found between codon and anticodon compared to the cognate pairings. The mismatch can reside in the first, second, or third position. Interactions with more than one mismatch are called noncognate (not shown). 

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).

Another pairing that occurs in tRNAs allows guanine to pair with uracil, e.g., G4 with U69. This was originally proposed to account for codon-anticodon interactions betweentRNA molecules and messenger RNA (Chapter 29). It is commonly called wobble pairing because the uracil must wobble away from its orientation in the normal Watson-Crick pair.27 37... 

The Code Was Deciphered with the Help of Synthetic Messengers The Code Is Highly Degenerate Wobble Introduces Ambiguity into Codon-Anticodon Interactions... 

In the translation process, codons in mRNA and anticodons in tRNA interact in an antiparallel manner such that the two 5 bases of the codon interact with two... 

The tertiary structure of all tRNAs are likewise similar. All known tRNAs are roughly L-shaped, with the anticodon on one end of the L and the acceptor stem on the other. Each stem of the L is made up of two of the stems of the cloverleaf, arranged so that the base pairs of each stem are stacked on top of each other. The parts of the molecule that are not base-paired are involved in other types of interactions, termed tertiary interactions. The tertiary structures of tRNAs thus reflect the dual functions of the molecule The anticodons are well-separated from the acceptor stems. This feature allows two tRNA molecules to interact with two codons that are adjacent on an mRNA molecule. See Figure 10-4. 

This can be accounted for by the wobble hypothesis it appears that when a codon in mRNA interacts with the anticodon, unconventional pairing can form between the base in the third position of the codon (3 end of triplet) and the first position of the anticodon. The unusual nucleoside inosine (Chap. 7) frequently occurs in the latter position, and it can pair with A, U, or C. The possibility of more than one type of pairing in this position accounts for the fact that when there is more than one codon for a single amino acid (called synonyms, see Table 17.1), the differences are usually in the third position only. 

Leucine has six codons, the largest number for any amino acid. According to the wobble hypothesis, a single tRNA can accommodate more than one codon. The wobble hypothesis allows for up to three different nucleotides, but only at the third position in the codon, to interact with a single nucleotide in the anticodon. The fact that there are six codons in leucine means that they must differ at positions other than the third, and they therefore could not be accommodated by a single anticodon in a particular tRNA molecule. 

At the ribosome, which travels along the mRNA, the tRNA molecule is bound such that its anticodon can interact with a nucleotide triplet on mRNA (the codon). If the anticodon is complementary to a codon triplet on the mRNA, the amino acid attached at the 3 -terminus of the tRNA is transferred to the amino terminus of the growing polypeptide chain if it is not complementanty, the tRNA is rejected and another one is checked for complementary. The whole process is repeated until the synthesis of the protein is completed. It is initiated, as well as terminated, by specific codons regulating this translation. 

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