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

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

Author information

1
Structural Biology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abstract

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.

PMID:
21940857
PMCID:
PMC3214010
DOI:
10.1126/science.1209307
[Indexed for MEDLINE]
Free PMC Article

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