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.

Discovery and characterization of noncanonical E2-conjugating enzymes / Abdul Rehman, Sa; Cazzaniga, C; Di Nisio, E; Antico, O; Knebel, A; Johnson, C; Şahin, At; Ibrahim, Pegf; Lamoliatte, F; Negri, R; Miratul Muqit, Mk; De Cesare, V.. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 10:13(2024). [10.1126/sciadv.adh0123]

Discovery and characterization of noncanonical E2-conjugating enzymes

Di Nisio E
Investigation
;
Negri R
Writing – Review & Editing
;
2024

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.
2024
E2-conjugating enzymes; ubiquitin; mass spectrometry
01 Pubblicazione su rivista::01a Articolo in rivista
Discovery and characterization of noncanonical E2-conjugating enzymes / Abdul Rehman, Sa; Cazzaniga, C; Di Nisio, E; Antico, O; Knebel, A; Johnson, C; Şahin, At; Ibrahim, Pegf; Lamoliatte, F; Negri, R; Miratul Muqit, Mk; De Cesare, V.. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 10:13(2024). [10.1126/sciadv.adh0123]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1707347
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