Fundamentals of Biochemical Engineering, Part 1 - Bailey J., Ollis D. 1989

Molecular Genetics and Regulatory Systems
Molecular Genetics
Post-Translational Modification of Proteins

The polypeptide resulting from mRNA Translation is frequently not yet in its mature, biologically active protein form. Sometimes, the N-terminal Methionine residue is cleaved from the protein post-translationally. In other instances, The oxidation of two Cysteine residues occurs, leading to The formation of a disulfide bond—a crucial factor in stabilizing the Tertiary Structure of the protein (Chap. 2). The attachment of carbohydrate residues to the side chains of asparagine, Serine, and Threonine yields Glycoproteins. Hydroxylation, phosphorylation, and Acetylation reactions are also employed in the chemical modification (Processing) of Polypeptides.

Certain polypeptides feature a short sequence (15–30 residues) of hydrophobic Amino Acids at the N-terminus. Such signal sequences play a major role in The transport of Proteins across Cell membranes. Secreted proteins typically contain these sequences. The prefix "pre-" is usually added to the names of proteins containing signal sequences (e.g., prelysozyme). The signal sequence is cleaved off during the transport of the preprotein across the membrane, resulting in the formation of a functionally active protein (Lysozyme, in our example).

Proteins may also contain other Amino acid sequences that are cleaved away when they are converted into their functionally active form. Alongside the protein secretion mechanisms mentioned above, such structural elements enable The Cell to carry out Protein Synthesis AND activate specific proteins at various locations within or outside the cell. The preproinsulin molecule, for instance, is constructed from an N-terminal signal sequence (24 amino acid residues), followed by a 21-residue sequence (B chain), then another 21-residue sequence (C chain), and finally a 30-residue C-terminal segment (A chain). The signal sequence is cleaved during secretion; the resulting proinsulin (A–C–B chains) is subsequently cleaved by Enzymes into Insulin, which consists of the A and B chains linked by two interchain Disulfide Bonds. There are no peptide bonds between the A and B chains in insulin (Fig. 6.8).