Areas of research

Protein N-terminal acetylation

Protein N-terminal acetylation is among the most common types of protein modifications occurring on approximately 50 % of all yeast proteins and more than 80 % of all human proteins. Surprisingly, there is yet no clear functional understanding of how N-terminal acetylation affects proteins in general, although recent data indicate roles in protein folding, turnover and subcellular targeting. N-terminal acetylation is a co-translational process occurring on the ribosomes and is considered irreversible. However, we recently identified the first human enzymes acting post-translationally. An N-terminal acetyltransferase (NAT) transfers an Acetyl group from Acetyl Coenzyme A to the alpha-amino group of the N-terminal amino acid residue of the protein. 
During the last two decades, all human NATs have been identified and characterized by our group. In humans as in yeast, three NAT complexes NatA, NatB and NatC are believed to perform most N-terminal acetylations. Each NAT complex is composed of specific subunits and acetylates a specific subset of substrates. A number of studies have described various aspects of N-terminal acetylation in humans, such as substrates, the molecular mechanisms, impact for protein fate, cellular roles, and connections to cancer and neurodegenerative disease. Through these studies, a complex and specific system of N-terminal acetylation has been revealed. The importance of N-terminal acetylation in human cell biology and disease is increasingly recognized.