Biochemistry and Molecular Biology - Belyasova, N.A. 2002

Molecular Foundations and Mechanisms of Heredity
Gene Expression
Post-Translational Protein Modification

Polypeptide molecules synthesized during Translation are frequently not mature, biologically active forms of Proteins. For them to acquire functional activity, various alterations in their Composition and Structure are required, collectively known as post-translational modification. The most common events of this type include chain Cleavage and shortening; phosphorylation, Acetylation, hydroxylation, and carboxylation of specific amino acid residues; Attachment of Peptides to Polysaccharides or Lipids; binding to prosthetic groups, etc.

An example of peptide chain shortening is the removal of the N-terminal formylmethionine (or Methionine), which is incorporated into all polypeptide molecules during Translation initiation. This event often occurs directly on Ribosomes early in translation.

Cleavage of precursor proteins frequently occurs during the assembly of complex bacteriophage capsids (T4, P2, λ, T5), as well as many proteolytic proteins, Hormones, and mammalian Neuropeptides. For instance, Insulin is synthesized during translation as a preproinsulin polypeptide and is converted into mature insulin following chain cleavage and the removal of both the N-terminal and internal segments (Chapter 21).

The binding of peptides to prosthetic groups can be illustrated by The formation of functionally active Hemoglobin. The α- and β-chains of hemoglobin produced during translation first assemble into an α₂β₂ structure, after which heme binds to the side chains of Amino Acids in both subunits. Pyruvate carboxylase undergoes a similar modification: for this enzyme to acquire activity, biotin must become covalently attached to specific amino acid side chains.

Modification of amino acid residues is a widespread phenomenon. Carboxylation of specific glutamic acid residues in proteins involved in Blood clotting enables the binding of Ca²⁺. Collagen formation requires the hydroxylation of specific Proline and Lysine residues. Phosphorylation and dephosphorylation of certain Serine, Threonine, and Tyrosine residues play a role in Metabolic Regulation.

Some proteins feature a short (15–35 residues) sequence of hydrophobic amino acids at the N-terminus, known as a "signal sequence." These sequences play a critical role in Protein Transport Across membranes: they are recognized by signal recognition particles within membranes, which mediate targeted protein translocation. During membrane transfer, the signal sequence is cleaved off by signal peptidase. As a result, the protein attains functional activity upon reaching its destination organelle (e.g., a lysosome) or the extracellular space. Frequently, protein transport across membranes occurs co-translationally with the participation of membrane-bound ribosomes (in eukaryotes, these are most commonly the membranes of the rough Endoplasmic reticulum). This process is referred to as co-translational transport.

Post-translational modification events expand the regulatory capacity of Cells over METABOLISM. Changes in the concentration or activity of Enzymes involved in protein modification lead to decreases or increases in protein levels, thereby altering the rates of corresponding cellular processes.