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Updated: May 29, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex
Daniel C Scott1, Julie K Monda, Eric J Bennett
1Structural Biology Department, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Science (New York, N.Y.)
|September 24, 2011
Summary
N-terminal acetylation of the Ubc12 enzyme directs protein interactions and promotes cullin neddylation. This study reveals how N-terminal acetylation guides Ubc12
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Many eukaryotic proteins undergo N-terminal acetylation, but its role in mediating protein interactions is poorly understood.
- The E2 enzyme Ubc12 and the E3 ligase Dcn1 are key components in the neddylation pathway, which modifies the Cul1 protein.
Purpose of the Study:
- To elucidate the structural mechanisms by which N-terminal acetylation of Ubc12 influences its interaction with E3 ligases.
- To define the role of N-terminal acetylation in the E3-dependent ligation of Nedd8 to Cul1.
Main Methods:
- The study employed structural, biochemical, biophysical, and genetic analyses.
- Key techniques included X-ray crystallography, enzyme activity assays, and mutational studies.
Main Results:
- N-terminal acetylation of Ubc12 dictates its specific ligation to Cul1 via the E3 ligase Dcn1.
- Structural analysis revealed that the N-acetyl-methionine of Ubc12 is buried in a hydrophobic pocket of Dcn1, facilitating cullin neddylation.
- Acetylation directs Ubc12-Dcn1 interactions and prevents charge repulsion at the N-terminus.
Conclusions:
- This research establishes a direct link between N-terminal acetylation and ubiquitin-like protein conjugation.
- A novel mechanism for N-terminal acetylation-dependent protein recognition is defined, highlighting its importance in regulating protein interactions and cellular processes.
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