Human Biochemistry, Volume 2 - Murray R. 1993

Structure, Function, and Replication of Information Macromolecules
Protein Synthesis and the Genetic Code
Transfer RNAs and Protein Synthesis

At least one type of tRNA exists for each of the 20 Amino Acids. All tRNA molecules share a remarkable degree of similarity both functionally and in their Spatial Structure. Their adaptor function becomes possible upon The formation of a specific complex between a tRNA molecule and a designated amino acid. Because Nucleic Acids possess no inherent affinity for the side chains of amino acids, mutual recognition must be mediated by a specialized protein molecule capable of simultaneously identifying both a specific tRNA molecule and its corresponding amino acid. To ensure such recognition and the accurate attachment of the appropriate amino acid to the tRNA, at least 20 specific Enzymes must exist. This recognition and attachment process occurs in two steps and is catalyzed by an enzyme unique to each of the 20 amino acids, belonging to the aminoacyl-tRNA synthetase Class. This enzyme forms an activated intermediate aminoacyl-AMP-enzyme complex (Fig. 40.1), which specifically recognizes the cognate tRNA molecule and transfers The amino acid residue to the 3'-hydroxyl group of the terminal adenosine. The amino acid remains ester-linked to the tRNA until it is incorporated into a specific position of the growing polypeptide chain of the protein precursor.

Now let us return to The structure of the tRNA molecule described in Chapter 37 and illustrated in Fig. 37.11. The thymidine-pseudouridine-cytidine (TΨC) arm is involved in binding aminoacyl-tRNA to the ribosome at the site of Protein Synthesis. The D arm is essential for the specific recognition of a given tRNA molecule by its corresponding aminoacyl-tRNA synthetase. The acceptor arm serves as the attachment site for the appropriate amino acid.

The anticodon region consists of 7 NUCLEOTIDES and recognizes the three-letter codon in mRNA (Fig. 40.2). Read from the 3' to the 5' end, The sequence of this region has the following structure: variable base, modified purine, the anticodon itself (x, y, z), pyrimidine, pyrimidine-5'. Note that the anticodon is read in the 3'→5' direction, whereas METABOLISM/28.html">The Genetic Code is read from 5' to 3', because the mRNA codon and the tRNA anticodon loop are antiparallel.

Fig. 40.1. Formation of aminoacyl-tRNA. A two-step reaction involving aminoacyl-tRNA synthetase leads to the formation of aminoacyl-tRNA. In the first reaction, an AMP-amino acid-enzyme complex is formed. The activated amino acid is transferred to the corresponding tRNA molecule. AMP and the enzyme are released, after which the enzyme can participate in the synthetase reaction once again.

The degeneracy of the genetic code primarily affects the third nucleotide of the codon and implies that base pairing between it and the corresponding nucleotide of the anticodon need not be strictly rigid. As already mentioned, this phenomenon is referred to as wobble or non-standard base pairing, because imprecise binding—the "wobble"—is permitted at the interaction site of the final codon nucleotide with the anticodon. For example, the two Arginine codons AGA and AGG can specifically bind to the same anticodon containing a uracil residue at the 5' end. Similarly, the three Glycine codons GGU, GGC, and GGA can pair with the CCI anticodon. Inosine (I) is another unusual (minor) base found in tRNA Structure.

Codon recognition by a tRNA molecule is independent of which amino acid is attached to its 3' end. This was demonstrated in an experiment in which radioactive Cysteine attached to a specific tRNA molecule (tRNA_cys) was chemically converted to Alanine. The anticodon region of the tRNA_cys itself remained unchanged. When such alanyl-tRNA_cys was used in the Translation of Hemoglobin mRNA, radioactive alanine was found in the Amino Acid Sequence at positions normally occupied by cysteine residues. This experiment demonstrated that the amino acid residue itself does not participate in specific codon recognition. As noted previously, the amino acid residues incorporated into the polypeptide chain do not make direct contact with the mRNA template at all.

Fig. 40.2. Codon-anticodon recognition. UUU is one of the codons for phenylalanine. A tRNA molecule "charged" with phenylalanine (Phe) contains a complementary AAA sequence in its anticodon region, which forms a complex with the three-base-pair codon. The anticodon region typically contains the following heptanucleotide sequence: a variable nucleotide (N); a modified purine (Pu*); an anticodon (X, Y, Z); two Pyrimidines (Py) (3'→5' orientation).