N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex

Science. 2011 Nov 4;334(6056):674-8. doi: 10.1126/science.1209307. Epub 2011 Sep 22.


Although many eukaryotic proteins are amino (N)-terminally acetylated, structural mechanisms by which N-terminal acetylation mediates protein interactions are largely unknown. Here, we found that N-terminal acetylation of the E2 enzyme, Ubc12, dictates distinctive E3-dependent ligation of the ubiquitin-like protein Nedd8 to Cul1. Structural, biochemical, biophysical, and genetic analyses revealed how complete burial of Ubc12's N-acetyl-methionine in a hydrophobic pocket in the E3, Dcn1, promotes cullin neddylation. The results suggest that the N-terminal acetyl both directs Ubc12's interactions with Dcn1 and prevents repulsion of a charged N terminus. Our data provide a link between acetylation and ubiquitin-like protein conjugation and define a mechanism for N-terminal acetylation-dependent recognition.

Publication types

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

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Cullin Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism*
  • NEDD8 Protein
  • Protein Binding
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitins / metabolism


  • Cullin 1
  • Cullin Proteins
  • Dcn1 protein, S cerevisiae
  • Multiprotein Complexes
  • NEDD8 Protein
  • NEDD8 protein, human
  • RUB1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • UBC12 protein, S cerevisiae
  • Ubiquitins
  • Ubiquitin-Protein Ligases

Associated data

  • PDB/3TDI
  • PDB/3TDU
  • PDB/3TDZ