Ubiquitin is a carbon dioxide-binding protein.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34559559.
- Also identified by DOI 10.1126/sciadv.abi5507 and PMC identifier 8462908.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The identification of CO<sub>2</sub>-binding proteins is crucial to understanding CO<sub>2</sub>-regulated molecular processes. CO<sub>2</sub> can form a reversible posttranslational modification through carbamylation of neutral N-terminal α-amino or lysine ε-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 CO<sub>2</sub>-binding protein. We use <sup>13</sup>C-NMR spectroscopy to demonstrate that CO<sub>2</sub> forms carbamates on the ubiquitin N terminus and ε-amino groups of lysines 6, 33, 48, and 63. We demonstrate that biologically relevant <i>p</i>CO<sub>2</sub> levels reduce ubiquitin conjugation at lysine-48 and down-regulate ubiquitin-dependent NF-κB pathway activation. Our results show that ubiquitin is a CO<sub>2</sub>-binding protein and demonstrates carbamylation as a viable mechanism by which mammalian cells can respond to fluctuating <i>p</i>CO<sub>2</sub>.