Protein alpha-N-acetylation studied by N-terminomics

Abstract

Cotranslational protein N-terminal modifications, including proteolytic maturation such as initiator methionine excision by methionine aminopeptidases and N-terminal blocking, occur universally. Protein alpha-N-acetylation, or the transfer of the acetyl moiety of acetyl-coenzyme A to nascent protein N-termini, catalysed by multisubunit N-terminal acetyltransferase complexes, generally takes place during protein translation. Nearly all protein modifications are known to influence different protein aspects such as folding, stability, activity and localization, and several studies have indicated similar functions for protein alpha-N-acetylation. However, until recently, protein alpha-N-acetylation remained poorly explored, mainly due to the absence of targeted proteomics technologies. The recent emergence of N-terminomics technologies that allow isolation of protein N-terminal peptides, together with proteogenomics efforts combining experimental and informational content have greatly boosted the field of alpha-N-acetylation. In this review, we report on such emerging technologies as well as on breakthroughs in our understanding of protein N-terminal biology. N-terminomics is a powerful tool for studying protein N-terminal modifications including protein N-terminal acetylation, an ubiquitous modification catalyzed by multi-subunit N-terminal acetyltransferase complexes. In this review, we highlight the recent advances made in this expanding field and provide an overview of the observed functional implications of alpha-N-acetylation and present state-of-the-art technologies, all permitting for a better understanding of N-terminal biology. © 2011 The Authors Journal compilation.