Molecular basis for N-terminal acetylation by the heterodimeric NatA complex

Glen Liszczak, Jacob M. Goldberg, Håvard Foyn, E. James Petersson, Thomas Arnesen, Ronen Marmorstein

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

N-terminal acetylation is ubiquitous among eukaryotic proteins and controls a myriad of biological processes. Of the N-terminal acetyltransferases (NATs) that facilitate this cotranslational modification, the heterodimeric NatA complex has the most diversity for substrate selection and modifies the majority of all N-terminally acetylated proteins. Here, we report the X-ray crystal structure of the 100-kDa holo-NatA complex from Schizosaccharomyces pombe, in the absence and presence of a bisubstrate peptide-CoA-conjugate inhibitor, as well as the structure of the uncomplexed Naa10p catalytic subunit. The NatA-Naa15p auxiliary subunit contains 13 tetratricopeptide motifs and adopts a ring-like topology that wraps around the NatA-Naa10p subunit, an interaction that alters the Naa10p active site for substrate-specific acetylation. These studies have implications for understanding the mechanistic details of other NAT complexes and how regulatory subunits modulate the activity of the broader family of protein acetyltransferases.

Original languageEnglish (US)
Pages (from-to)1098-1105
Number of pages8
JournalNature Structural and Molecular Biology
Volume20
Issue number9
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Liszczak, G., Goldberg, J. M., Foyn, H., Petersson, E. J., Arnesen, T., & Marmorstein, R. (2013). Molecular basis for N-terminal acetylation by the heterodimeric NatA complex. Nature Structural and Molecular Biology, 20(9), 1098-1105. https://doi.org/10.1038/nsmb.2636