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Science 334 (6056): 674-678

Copyright © 2011 by the American Association for the Advancement of Science

N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex

Daniel C. Scott,1,2 Julie K. Monda,1 Eric J. Bennett,3,* J. Wade Harper,3 Brenda A. Schulman1,2,{dagger}

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.

1 Structural Biology Department, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
2 Howard Hughes Medical Institute, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
3 Cell Biology Department, Harvard Medical School, Boston, MA 02115, USA.

* Present address: Division of Biological Sciences, University of California–San Diego, La Jolla, CA 92093, USA.

{dagger} To whom correspondence should be addressed. E-mail: brenda.schulman{at}

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