Description
Virginia De CesareMRC Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee,
Dundee, UK
Ubiquitin conjugating enzymes (E2s) are central to ubiquitin attachment, dictating the cellular ubiquitylation landscape through interactions with multiple ubiquitin ligases (E3s). While ubiquitylation typically targets lysine side chains, recent work has revealed other non-canonical forms of ubiquitylation. However, the role of E2 enzymes in enabling non-canonical ubiquitylation
is not understood. Hence, we developed a Matrix-assisted laser desorption/ionization-time of flight Mass Spectrometry (MALDI-TOF/MS) assay to screen and identify E2 enzymes capable of catalyzing ubiquitin attachment via ester linkages. Excitingly, we discover the UBE2Q family of E2s to be capable of conjugating ubiquitin to serine, threonine, glucose, and complex sugars in an
E3-independent manner. UBE2Qs are structurally distinct from other E2s as they lack the canonical Histidine-Proline-Asparagine (HPN) triad but feature an extended N-terminus. I will present our recent work where we employ structural and biochemical analyses to determine the mechanistic basis of non-canonical ubiquitylation mediated by UBE2Q. We anticipate that the discovery of E2s
with non-canonical activity will have profound and wide-ranging impact on the expansion of the ubiquitylation landscape and, consequently, toward the understanding of ubiquitin-mediated biological processes.
| Period | 29 Sept 2024 |
|---|---|
| Event title | Ubiquitin and ubiquitin-like proteins in health and disease |
| Event type | Workshop |
| Location | Drubrovnik, CroatiaShow on map |