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Updated: Jun 20, 2025
12:11
Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization
Published on: February 27, 2020
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Biochemical and Structural Consequences of NEDD8 Acetylation
Simon Maria Kienle1, Tobias Schneider1, Christine Bernecker1
1Departments of Biology and Chemistry, Konstanz Research School Chemical Biology, University of Konstanz, Universitätsstr. 10, 78457, Konstanz, Germany.
Chembiochem : a European Journal of Chemical Biology
|July 18, 2024
Summary
Acetylation of the ubiquitin-like protein NEDD8, particularly at K11, impacts its function by affecting conjugation enzymes. This study identifies p300 as a specific NEDD8 acetyltransferase.
Area of Science:
- Biochemistry
- Molecular Biology
- Posttranslational Modifications
Background:
- The ubiquitin-like protein NEDD8 undergoes posttranslational modifications, including lysine acetylation, similar to ubiquitin.
- The functional and structural consequences of NEDD8 acetylation are not well understood compared to ubiquitin.
Purpose of the Study:
- To investigate the biochemical and structural effects of site-specific NEDD8 acetylation.
- To identify the enzymes responsible for NEDD8 acetylation.
Main Methods:
- Generation of site-specifically mono-acetylated NEDD8 variants using genetic code expansion.
- Assays to assess the impact of acetylation on NEDD8 conjugation with UBE2M and UBE2F.
- Structural analysis to understand conformational changes.
Main Results:
- Acetylation, especially at K11, negatively affects NEDD8 usage by UBE2M and UBE2F.
- Electrostatic and steric effects, leading to conformational changes, are likely responsible for reduced enzyme usage.
- Evidence suggests p300 functions as a site-specific NEDD8 acetyltransferase.
Conclusions:
- NEDD8 acetylation, particularly K11 acetylation, modulates its interaction with conjugation machinery.
- Conformational changes induced by acetylation impact NEDD8's biological activity.
- p300 is identified as a key enzyme in the NEDD8 acetylation pathway.
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