Posttranslational Modification of Proteins

The process of making a protein involves more than just translation of the nucleic acid sequence. The product of translation is a polypeptide chain (a polymer of amino acids) that must be folded into its proper three-dimensional form and in some cases, disulfide bonds must be formed. The protein may also be modified in the following ways.

> 1. Occasionally, some amino acids in the protein may be chemically modified. In collagen (a protein found in cartilage), for example, some proline residues are modified to hydroxyproline, which can help stabilize the three-dimensional shape of the protein via hydrogen bonds. Lysine residues in collagen can be hydroxylated, too (see here), thus providing attachment sites for polysaccharides. Additionally, lysine residues in collagen can be oxidized to aldehyde derivatives, which can then cross-link with other lysine residues (modified or unmodified).

> 2. More often, covalent modification of a polypeptide involves cleaving a portion of the polypeptide away with a specific enzyme(s). For example, Figure 5.21 shows how insulin is made as a single polypeptide precursor called preproinsulin. Preproinsulin is transported to the membrane where a portion of the polypeptide, called the leader sequence, is cleaved, yielding proinsulin. Proinsulin folds into its proper three-dimensional structure and disulfide bonds form between the cysteines. A segment of amino acids between the disulfide bonds is cleaved, yielding two polypeptide chains held together by disulfide bonds.

> Insulin is secreted in this manner because it functions outside the cells in which it is synthesized. Thus, the leader sequence helps preproinsulin be transported through the hydrophobic cell membrane. Additionally, proinsulin is an inactive form of the protein, so it can be stored in tissues in high concentration, then rapidly converted to insulin when needed by the body.

See also: Proteins, Amino Acids, Peptide Hormone Synthesis (from Chapter 23), Covalent Modifications to Regulate Enzyme Activity (from Chapter 11), Covalent Modification of Proteins (from Chapter 27)

INTERNET LINK: The Role of Enzymes in Biological Reactions