Ubiquitin is a carbon dioxide-binding protein

Linthwaite, V.L.; Pawloski, W.; Pegg, H.B.; Townsend, P.D.; Thomas, M.J.; Brown, A.P.; Hodgson, D.R.W.; Lorimer, G.H.; Fushman, D.; Cann, M.J.

Abstract

The identification of CO2-binding proteins is crucial to understanding CO2-regulated molecular processes. CO2 can form a reversible posttranslational modification through carbamylation of neutral N-terminal -amino or lysine -amino groups. We have previously developed triethyloxonium (TEO) ion as a chemical proteomics tool for covalent trapping of carbamates, and here, we deploy TEO to identify ubiquitin as a mammalian CO2-binding protein. We use 13C-NMR spectroscopy to demonstrate that CO2 forms carbamates on the ubiquitin N terminus and -amino groups of lysines 6, 33, 48, and 63. We demonstrate that biologically relevant pCO2 levels reduce ubiquitin conjugation at lysine-48 and down-regulate ubiquitin-dependent NF-B pathway activation. Our results show that ubiquitin is a CO2-binding protein and demonstrates carbamylation as a viable mechanism by which mammalian cells can respond to fluctuating pCO2

Citation

Linthwaite, V., Pawloski, W., Pegg, H., Townsend, P., Thomas, M., Brown, A., Hodgson, D., Lorimer, G., Fushman, D., & Cann, M. (2021). Ubiquitin is a carbon dioxide-binding protein. Science Advances, 7(39), Article eabi5507. https://doi.org/10.1126/sciadv.abi5507

• Journal Article Type: Article
• Acceptance Date: Nov 26, 2020
• Online Publication Date: Sep 24, 2021
• Publication Date: 2021-09
• Deposit Date: Nov 26, 2020
• Publicly Available Date: Oct 7, 2021
• Journal: Science Advances
• Publisher: American Association for the Advancement of Science
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 39
• Article Number: eabi5507
• DOI: https://doi.org/10.1126/sciadv.abi5507
• Public URL: https://durham-repository.worktribe.com/output/1256588