Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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}stjude.org


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
N-terminal Acetylation Stabilizes N-terminal Helicity in Lipid- and Micelle-bound {alpha}-Synuclein and Increases Its Affinity for Physiological Membranes.
I. Dikiy and D. Eliezer (2014)
J. Biol. Chem. 289, 3652-3665
   Abstract »    Full Text »    PDF »
Building and remodelling Cullin-RING E3 ubiquitin ligases.
J. R. Lydeard, B. A. Schulman, and J. W. Harper (2013)
EMBO Rep. 14, 1050-1061
   Abstract »    Full Text »    PDF »
Coamplification and Cooperation: Toward Identifying Biologically Relevant Oncogenes.
G. Huang and B. Singh (2013)
Clin. Cancer Res. 19, 5549-5551
   Abstract »    Full Text »    PDF »
Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog.
G. Liszczak and R. Marmorstein (2013)
PNAS 110, 14652-14657
   Abstract »    Full Text »    PDF »
The emerging family of CULLIN3-RING ubiquitin ligases (CRL3s): cellular functions and disease implications.
P. Genschik, I. Sumara, and E. Lechner (2013)
EMBO J. 32, 2307-2320
   Abstract »    Full Text »    PDF »
The Cyclomodulin Cycle Inhibiting Factor (CIF) Alters Cullin Neddylation Dynamics.
T. B. Toro, J. I. Toth, and M. D. Petroski (2013)
J. Biol. Chem. 288, 14716-14726
   Abstract »    Full Text »    PDF »
N-terminal acetylation of the yeast Derlin Der1 is essential for Hrd1 ubiquitin-ligase activity toward luminal ER substrates.
D. Zattas, D. J. Adle, E. M. Rubenstein, and M. Hochstrasser (2013)
Mol. Biol. Cell 24, 890-900
   Abstract »    Full Text »    PDF »
Protein N-terminal Acetyltransferases Act as N-terminal Propionyltransferases In Vitro and In Vivo.
H. Foyn, P. Van Damme, S. I. Stove, N. Glomnes, R. Evjenth, K. Gevaert, and T. Arnesen (2013)
Mol. Cell. Proteomics 12, 42-54
   Abstract »    Full Text »    PDF »
Post-translational modification of cardiac proteasomes: functional delineation enabled by proteomics.
S. B. Scruggs, N. C. Zong, D. Wang, E. Stefani, and P. Ping (2012)
Am J Physiol Heart Circ Physiol 303, H9-H18
   Abstract »    Full Text »    PDF »
Obscurin and KCTD6 regulate cullin-dependent small ankyrin-1 (sAnk1.5) protein turnover.
S. Lange, S. Perera, P. Teh, and J. Chen (2012)
Mol. Biol. Cell 23, 2490-2504
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882