Discovery and characterization of non-canonical E2 conjugating enzymes

TY - UNPB

T1 - Discovery and characterization of non-canonical E2 conjugating enzymes

AU - Rehman, Syed Arif Abdul

AU - Di Nisio, Elena

AU - Cazzaniga, Chiara

AU - Antico, Odetta

AU - Knebel, Axel

AU - Johnson, Clare

AU - Lamoliatte, Fred

AU - Negri, Rodolfo

AU - Muqit, Miratul

AU - De Cesare, Virginia

PY - 2023/3/5

Y1 - 2023/3/5

N2 - 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 fundamental for maintaining cellular homeostasis and impacts almost all cellular process. By interacting with multiple E3 ligases, E2s direct the ubiquitylation landscape within the cell. Since its discovery, ubiquitylation has been regarded as a post-translational modification that specifically targets lysine side chains (canonical ubiquitylation). We used MALDI-TOF Mass Spectrometry to discover and characterize a family of E2s that are instead able to conjugate ubiquitin to serine and/or threonine. We employed protein modelling and prediction tools to identify the catalytic determinants that these E2s use to interact with ubiquitin as well as their substrates. Our results join a stream of recent literature that challenges the definition of ubiquitylation as an exquisitely lysine-specific modification and provide crucial insights into the missing E2 element responsible for non-canonical ubiquitylation.

AB - 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 fundamental for maintaining cellular homeostasis and impacts almost all cellular process. By interacting with multiple E3 ligases, E2s direct the ubiquitylation landscape within the cell. Since its discovery, ubiquitylation has been regarded as a post-translational modification that specifically targets lysine side chains (canonical ubiquitylation). We used MALDI-TOF Mass Spectrometry to discover and characterize a family of E2s that are instead able to conjugate ubiquitin to serine and/or threonine. We employed protein modelling and prediction tools to identify the catalytic determinants that these E2s use to interact with ubiquitin as well as their substrates. Our results join a stream of recent literature that challenges the definition of ubiquitylation as an exquisitely lysine-specific modification and provide crucial insights into the missing E2 element responsible for non-canonical ubiquitylation.

U2 - 10.1101/2023.03.05.531151

DO - 10.1101/2023.03.05.531151

M3 - Preprint

BT - Discovery and characterization of non-canonical E2 conjugating enzymes

PB - BioRxiv

ER -