Having seen that each amino acid is first coupled to specific tRNA molecules, we now turn to the mechanism that joins these amino acids together to form proteins. The fundamental reaction of protein synthesis is the formation of a peptide bond between the carboxyl group at the end of a growing polypeptide chain and a free amino group on an incoming amino acid. Consequently, a protein is synthesized stepwise from its N-terminal end to its C-terminal end. Throughout the entire process, the growing carboxyl end of the polypeptide chain remains activated by its covalent attachment to a tRNA molecule (forming a peptidyl-tRNA). Each
Figure 6–57 Hydrolytic editing.
Aminoacyl tRNA synthetases correct their own coupling errors through hydrolytic editing of incorrectly attached amino acids. As described in the text, the correct amino acid is rejected by the editing site.
The error-correction process performed by DNA polymerase has similarities; however, it differs because the removal process depends strongly on a mispairing with the template (see Figure 5–8).  (P, polymerization site; E, editing site.)
Figure 6–58 The recognition of a tRNA molecule by its aminoacyl-tRNA synthetase. For this tRNA (tRNAGln), specific nucleotides in both the anticodon (dark blue) and the amino acid-accepting arm (green) allow the correct tRNA to be recognized by the synthetase enzyme (yellow-green). A bound ATP molecule is yellow. (Courtesy of Tom Steitz;  PDB code: 1QRS.) peptidyl-tRNA attached to C-terminus of the growing polypeptide chain new peptidyl-tRNA molecule attached to C-terminus of the growing polypeptide chain
Figure 6–59 The incorporation of an amino acid into a protein. A polypeptide chain grows by the stepwise addition of amino acids to its C-terminal end. The formation of each peptide bond is energetically favorable because the growing C-terminus has been activated by the covalent attachment of a tRNA molecule. The peptidyl-tRNA linkage that activates the growing end is regenerated during each addition. The amino acid side chains have been abbreviated as R1, R2, R3, and R4; as a reference point, all of the atoms in the second amino acid in the polypeptide chain are shaded gray. The figure shows the addition of the fourth amino acid (red) to the growing chain.
addition disrupts this high-energy covalent linkage, but immediately replaces it with an identical linkage on the most recently added amino acid (Figure 6–59). In this way, each amino acid added carries with it the activation energy for the addition of the next amino acid rather than the energy for its own addition—an example of the “head growth” type of polymerization described in Figure 2–44.
The RNA Message Is Decoded in Ribosomes
The synthesis of proteins is guided by information carried by mRNA molecules. To maintain the correct reading frame and to ensure accuracy (about 1 mistake every 10,000 amino acids), protein synthesis is performed in the ribosome, a complex catalytic machine made from more than 50 different proteins (the ribosomal proteins) and several RNA molecules, the ribosomal RNAs (rRNAs). A typical eukaryotic cell contains millions of ribosomes in its cytoplasm (Figure 6–60). The large and small ribosome subunits are assembled at the nucleolus, where newly transcribed and modified rRNAs associate with the ribosomal proteins that have been transported into the nucleus after their synthesis in the cytoplasm. These two ribosomal subunits are then exported to the cytoplasm, where they join together to synthesize proteins.