Many proteins are acetylated in living cells, both co- and post-translationally, and at least for eukaryotic proteins, acetylation is the most common covalent modification. Acetylation of proteins is catalyzed by a wide range of acetyltransferases that transfer acetyl groups from acetyl-Coenzyme A to either the α-amino group of amino-terminal residues or to the ε-amino group of lysine residues at various positions.
Amino-terminal acetylation occurs co-translationally on the N-termini of nascent polypeptides in a majority of all eukaryotic proteins and post-translationally on prokaryotic ribosomal proteins and on processed eukaryotic regulatory peptides. Amino-terminal acetylation occurs on approximately 85% of eukaryotic proteins, but is rare for prokaryotic proteins. ε-Lysine acetylation take place post-translationally on histones, high mobility group (HMG) proteins, transcription factors, nuclear receptors, and α-tubulin. Acetylation affects many protein functions, including enzymatic activity, stability, DNA binding, protein-protein interaction, and peptide-receptor recognition.
Proteins susceptible to amino-terminal acetylation have a variety of different amino-terminal sequences, with no simple consensus motifs and no dependence on a single type of residue due to the presence of multiple N-acetyltransferases (NATs). Each NAT acts on different groups of amino-acid sequences and whose specificity is determined by two or more residues at the amino-terminal positions. Unlike the situation for histones and other proteins with acetylated ε-lysine residues, amino-terminal modifications are irreversible.
We have solved the crystal structure of human amino-terminal acetyltransferase NAT13 in complex with coenzyme A. The function of this enzyme in the eukaryotic cells remains to be discovered.
