Nature Communications (Jan 2025)

Illuminating the impact of N-terminal acetylation: from protein to physiology

  • Nina McTiernan,
  • Ine Kjosås,
  • Thomas Arnesen

DOI
https://doi.org/10.1038/s41467-025-55960-5
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 15

Abstract

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Abstract N-terminal acetylation is a highly abundant protein modification in eukaryotic cells. This modification is catalysed by N-terminal acetyltransferases acting co- or post-translationally. Here, we review the eukaryotic N-terminal acetylation machinery: the enzymes involved and their substrate specificities. We also provide an overview of the impact of N-terminal acetylation, including its effects on protein folding, subcellular targeting, protein complex formation, and protein turnover. In particular, there may be competition between N-terminal acetyltransferases and other enzymes in defining protein fate. At the organismal level, N-terminal acetylation is highly influential, and its impairment was recently linked to cardiac dysfunction and neurodegenerative diseases.