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

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.

Authors:
; ; ; ;  [1];  [2]
  1. (Harvard-Med)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OTHERINDUSTRYNIHHHMI
OSTI Identifier:
1039453
Resource Type:
Journal Article
Journal Name:
Science
Additional Journal Information:
Journal Volume: 334; Journal Issue: 11, 2011; Journal ID: ISSN 0036-8075
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ACETYLATION; ENZYMES; GENETICS; PROTEINS

Citation Formats

Scott, Daniel C., Monda, Julie K., Bennett, Eric J., Harper, J. Wade, Schulman, Brenda A., and SJCH). N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex. United States: N. p., 2012. Web. doi:10.1126/science.1209307.
Scott, Daniel C., Monda, Julie K., Bennett, Eric J., Harper, J. Wade, Schulman, Brenda A., & SJCH). N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex. United States. doi:10.1126/science.1209307.
Scott, Daniel C., Monda, Julie K., Bennett, Eric J., Harper, J. Wade, Schulman, Brenda A., and SJCH). Thu . "N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex". United States. doi:10.1126/science.1209307.
@article{osti_1039453,
title = {N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex},
author = {Scott, Daniel C. and Monda, Julie K. and Bennett, Eric J. and Harper, J. Wade and Schulman, Brenda A. and SJCH)},
abstractNote = {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.},
doi = {10.1126/science.1209307},
journal = {Science},
issn = {0036-8075},
number = 11, 2011,
volume = 334,
place = {United States},
year = {2012},
month = {10}
}