Molecular Biology: Protein Structure and Functions - Stepanov V.M. 2005

Post-translational protein modification
Processing of the amino-terminal region of a protein

In many Proteins, the amino-terminal region undergoes modification. As is well known, the Translation-initiating Methionine residue is formylated in prokaryotic proteins, as well as in Cell/35.html">Mitochondria and METABOLISM/14.html">Chloroplasts. The N-formyl group is subsequently removed by the enzyme formylase. In eukaryotes, translation is initiated by methionine. Once the peptide chain—still bound to the ribosome—reaches a length of approximately 20 amino acid residues, the initiating methionine may be cleaved off by a specific aminopeptidase. (However, this is not mandatory, and roughly half of animal cytoplasmic proteins retain their amino-terminal methionine.)

Among other N-terminal residues, relatively small ones—such as Alanine, Serine, and Threonine—predominate. This is likely due to the specific Properties of the aminopeptidase, which preferentially cleaves off the N-terminal methionine if it is followed by an amino acid with a small side chain. In cases where The amino acid following the terminal methionine possesses a bulky radical, the methionine is not removed and thus persists at the amino terminus of the protein.

There is reason to believe that The Nature of the N-terminal amino acid is somehow linked to the protein's resistance to intracellular proteolysis. This presumably also explains the prevalence of amino-terminal blocking via Acetylation: in total, the amino terminus is acetylated in approximately 50% of soluble proteins in mammalian Cells. In this reaction, catalyzed by N-a-acetyltransferase, acetyl-coenzyme A serves as the acetyl group donor. The most common N-terminal residues found in eukaryotic proteins are acetylserine, acetylalanine, and acetylmethionine. At the same time, an enzyme is known that is capable of cleaving an acetylated amino acid (such as acetylalanine) from N-a-acetylated proteins. Crucially, these modifications ensure a high diversity of amino termini in polypeptide chains, which, in the absence of such reactions, would invariably start with methionine. It is also possible that the removal of the N-terminal methionine is important because it allows for the recycling of this initiating amino acid, The Biosynthesis of which is quite energetically demanding.