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Abstract
E2-conjugating enzymes (E2s) play a central role in the enzymatic cascade that leads to the attachment of ubiquitin to a substrate. This process, termed ubiquitylation, is required to maintain cellular homeostasis and affects almost all cellular process. By interacting with multiple E3 ligases, E2s dictate the ubiquitylation landscape within the cell. Since its discovery, ubiquitylation has been regarded as a posttranslational modification that specifically targets lysine side chains (canonical ubiquitylation). We used Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry to identify and characterize a family of E2s that are instead able to conjugate ubiquitin to serine and/or threonine. We used structural modeling and prediction tools to identify the key activity determinants that these E2s use to interact with ubiquitin as well as their substrates. Our results unveil the missing E2s necessary for noncanonical ubiquitylation, underscoring the adaptability and versatility of ubiquitin modifications.
Original language | English |
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Article number | adh0123 |
Number of pages | 18 |
Journal | Science Advances |
Volume | 10 |
Issue number | 13 |
Early online date | 27 Mar 2024 |
DOIs | |
Publication status | Published - 29 Mar 2024 |
Keywords
- Ubiquitin-Conjugating Enzymes/chemistry
- Ubiquitin-Protein Ligases/metabolism
- Ubiquitination
- Ubiquitin/metabolism
- Protein Processing, Post-Translational
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Dive into the research topics of 'Discovery and characterization of noncanonical E2-conjugating enzymes'. Together they form a unique fingerprint.Projects
- 1 Active
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Assessing physiological relevance, biological roles and molecular mechnisms of non-canonical ubiquitination
De Cesare, V. (Investigator)
1/10/21 → 30/09/26
Project: Research
Research output
- 3 Citations
- 1 Preprint
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Discovery and characterization of non-canonical E2 conjugating enzymes
Rehman, S. A. A., Di Nisio, E., Cazzaniga, C., Antico, O., Knebel, A., Johnson, C., Lamoliatte, F., Negri, R., Muqit, M. & De Cesare, V. (Lead / Corresponding author), 5 Mar 2023, BioRxiv, 40 p.Research output: Working paper/Preprint › Preprint
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