BIOCHEMISTRY - L. Stryer - 1984

VOLUME 3

Part IV INFORMATION

CHAPTER 26. THE GENETIC CODE AND THE RELATIONSHIP BETWEEN GENES AND PROTEINS

Chapter 25 described The Role of Messenger RNA as an intermediary between a Gene and its polypeptide product. In this chapter, we trace the further flow of information from gene to protein. At the center of attention is METABOLISM/28.html">The Genetic Code, which relates The base sequence of DNA (or its corresponding transcript) to the Amino Acid Sequence of a protein. The code is universal for all organisms and is striking in its simplicity. Three bases, constituting a codon, determine a single amino acid. Codons are read sequentially by Transfer RNA (tRNA) molecules, which act as adapters in Protein Synthesis. The complete deciphering of the genetic code in the 1960s stands as one of the crowning achievements of modern biology.

26.1. Transfer RNA is the Adapter Molecule in Protein Synthesis

We have already seen that mRNA serves as the template for protein synthesis. How does it direct the assembly of Amino Acids in the correct order? In 1958, Francis Crick wrote:

“One of the early suggestions, rather a naive one, was that RNA would assume a configuration capable of forming twenty different 'cavities,' one for the side chain of each of the twenty amino acids. If this were so, one could try to run the problem in reverse, attempting to deduce the required RNA configuration by trying to reconstruct the shape of these cavities. All such attempts ended in failure. Physicochemical considerations likewise provide no grounds for considering this assumption plausible.”

Crick pointed out that RNA lacks protruding hydrophobic surfaces to distinguish valine from leucine and isoleucine, and that it does not contain suitably positioned charged groups to differentiate between positively and negatively charged amino acid side chains. Crick then proposed a fundamentally different mechanism for mRNA recognition:

“RNA is primarily a sequence of hydrogen-bonding regions. Therefore, regardless of what specifically binds to the template in a specific manner, the binding evidently occurs via Hydrogen bond formation. Consequently, it is natural to suppose that Amino acids are carried to the template by adapter molecules, and that the adapter itself corresponds to RNA. In the simplest case, 20 adapters would be required, one for each amino acid.” This pioneering hypothesis soon became established fact. The adapter role in Protein synthesis is played by tRNA. The Structure of these remarkable adapter molecules and the reactions in which they participate are examined in detail in the next chapter. Here, it suffices to note that tRNA possesses an amino acid attachment site and a template-recognition site (Figs. 26.1 and 26.2). A tRNA molecule transports a specific amino acid in an activated form to the site of protein synthesis. The carboxyl group of The amino acid is linked via an ester bond to either the 3'-hydroxyl or the 2'-hydroxyl group of the ribose residue located at the 3' end of the tRNA chain. During protein synthesis, the attached amino acid can shift between the 2'- and 3'-hydroxyl groups and back. The attachment of an amino acid to tRNA to form aminoacyl-tRNA is catalyzed by a specialized enzyme called aminoacyl-tRNA synthetase (or activating enzyme). This Esterification reaction is driven by the energy of ATP. For each of the 20 amino acids, there is at least one specific synthetase. The template-recognition site in tRNA is a sequence of three bases called the anticodon (Fig. 26.2). The anticodon of tRNA recognizes the codon, i.e., the complementary three-base sequence in mRNA.

Class="center">Fig. 26.1. Attachment of an amino acid (shown in red) to a tRNA molecule. The amino acid is linked by an ester bond to the 3'-hydroxyl group of the terminal adenosine of RNA. A tRNA molecule carrying a covalently attached amino acid is called aminoacyl-tRNA or “charged” tRNA, whereas tRNA without an amino acid is called “uncharged”

Fig. 26.2. Schematic drawing of aminoacyl-tRNA, showing the amino acid attachment site and the anticodon (template-recognition site)