Structure and Mechanism of Acetylation by the N-Terminal Dual Enzyme NatA/Naa50 Complex

Structure. 2019 Jul 2;27(7):1057-1070.e4. doi: 10.1016/j.str.2019.04.014. Epub 2019 May 30.

Abstract

NatA co-translationally acetylates the N termini of over 40% of eukaryotic proteins and can associate with another catalytic subunit, Naa50, to form a ternary NatA/Naa50 dual enzyme complex (also called NatE). The molecular basis of association between Naa50 and NatA and the mechanism for how their association affects their catalytic activities in yeast and human are poorly understood. Here, we determined the X-ray crystal structure of yeast NatA/Naa50 as a scaffold to understand coregulation of NatA/Naa50 activity in both yeast and human. We find that Naa50 makes evolutionarily conserved contacts to both the Naa10 and Naa15 subunits of NatA. These interactions promote catalytic crosstalk within the human complex, but do so to a lesser extent in the yeast complex, where Naa50 activity is compromised. These studies have implications for understanding the role of the NatA/Naa50 complex in modulating the majority of the N-terminal acetylome in diverse species.

Keywords: N-terminal acetylation; Naa50; NatA; NatE; X-ray crystallography; protein complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyl Coenzyme A / chemistry
  • Acetyl Coenzyme A / metabolism
  • Acetylation
  • Acetyltransferases / chemistry*
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Animals
  • Catalytic Domain
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kinetics
  • Models, Molecular
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • N-Terminal Acetyltransferase A / chemistry*
  • N-Terminal Acetyltransferase A / genetics
  • N-Terminal Acetyltransferase A / metabolism
  • N-Terminal Acetyltransferase E / chemistry*
  • N-Terminal Acetyltransferase E / genetics
  • N-Terminal Acetyltransferase E / metabolism
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Protein Processing, Post-Translational*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sf9 Cells
  • Spodoptera
  • Substrate Specificity

Substances

  • Isoenzymes
  • Multienzyme Complexes
  • NAA15 protein, human
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Acetyl Coenzyme A
  • Acetyltransferases
  • NatA protein, S cerevisiae
  • N-Terminal Acetyltransferase A
  • NAA10 protein, human
  • N-Terminal Acetyltransferase E
  • NAA50 protein, human