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

Publication Type:

Journal Article

Authors:

Scott, Daniel C; Monda, Julie K; Bennett, Eric J; Harper, J Wade; Schulman, Brenda A

Source:

Science, Volume 334, Issue 6056, p.674-8 (2011)

Keywords:

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

Abstract:

<p>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.</p>