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Ubiquitin is a carbon dioxide–binding protein
The identification of CO(2)-binding proteins is crucial to understanding CO(2)-regulated molecular processes. CO(2) 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) io...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462908/ https://www.ncbi.nlm.nih.gov/pubmed/34559559 http://dx.doi.org/10.1126/sciadv.abi5507 |
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author | Linthwaite, Victoria L. Pawloski, Wes Pegg, Hamish B. Townsend, Philip D. Thomas, Michael J. So, Victor K. H. Brown, Adrian P. Hodgson, David R. W. Lorimer, George H. Fushman, David Cann, Martin J. |
author_facet | Linthwaite, Victoria L. Pawloski, Wes Pegg, Hamish B. Townsend, Philip D. Thomas, Michael J. So, Victor K. H. Brown, Adrian P. Hodgson, David R. W. Lorimer, George H. Fushman, David Cann, Martin J. |
author_sort | Linthwaite, Victoria L. |
collection | PubMed |
description | The identification of CO(2)-binding proteins is crucial to understanding CO(2)-regulated molecular processes. CO(2) 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(2)-binding protein. We use (13)C-NMR spectroscopy to demonstrate that CO(2) forms carbamates on the ubiquitin N terminus and ε-amino groups of lysines 6, 33, 48, and 63. We demonstrate that biologically relevant pCO(2) levels reduce ubiquitin conjugation at lysine-48 and down-regulate ubiquitin-dependent NF-κB pathway activation. Our results show that ubiquitin is a CO(2)-binding protein and demonstrates carbamylation as a viable mechanism by which mammalian cells can respond to fluctuating pCO(2). |
format | Online Article Text |
id | pubmed-8462908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-84629082021-10-01 Ubiquitin is a carbon dioxide–binding protein Linthwaite, Victoria L. Pawloski, Wes Pegg, Hamish B. Townsend, Philip D. Thomas, Michael J. So, Victor K. H. Brown, Adrian P. Hodgson, David R. W. Lorimer, George H. Fushman, David Cann, Martin J. Sci Adv Biomedicine and Life Sciences The identification of CO(2)-binding proteins is crucial to understanding CO(2)-regulated molecular processes. CO(2) 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(2)-binding protein. We use (13)C-NMR spectroscopy to demonstrate that CO(2) forms carbamates on the ubiquitin N terminus and ε-amino groups of lysines 6, 33, 48, and 63. We demonstrate that biologically relevant pCO(2) levels reduce ubiquitin conjugation at lysine-48 and down-regulate ubiquitin-dependent NF-κB pathway activation. Our results show that ubiquitin is a CO(2)-binding protein and demonstrates carbamylation as a viable mechanism by which mammalian cells can respond to fluctuating pCO(2). American Association for the Advancement of Science 2021-09-24 /pmc/articles/PMC8462908/ /pubmed/34559559 http://dx.doi.org/10.1126/sciadv.abi5507 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Linthwaite, Victoria L. Pawloski, Wes Pegg, Hamish B. Townsend, Philip D. Thomas, Michael J. So, Victor K. H. Brown, Adrian P. Hodgson, David R. W. Lorimer, George H. Fushman, David Cann, Martin J. Ubiquitin is a carbon dioxide–binding protein |
title | Ubiquitin is a carbon dioxide–binding protein |
title_full | Ubiquitin is a carbon dioxide–binding protein |
title_fullStr | Ubiquitin is a carbon dioxide–binding protein |
title_full_unstemmed | Ubiquitin is a carbon dioxide–binding protein |
title_short | Ubiquitin is a carbon dioxide–binding protein |
title_sort | ubiquitin is a carbon dioxide–binding protein |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462908/ https://www.ncbi.nlm.nih.gov/pubmed/34559559 http://dx.doi.org/10.1126/sciadv.abi5507 |
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