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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.

SUBMITTER: Scott DC

PROVIDER: S-EPMC3214010 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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

Scott Daniel C DC Monda Julie K JK Bennett Eric J EJ Harper J Wade JW Schulman Brenda A BA

Science (New York, N.Y.) 20110922 6056

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 ...[more]

PMID: 21940857

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