Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions
Coenzyme A (CoA) is a key cellular metabolite known for its diverse functions in metabolism and regulation of gene expression. CoA was recently shown to play an important antioxidant role under various cellular stress conditions by forming a disulfide bond with proteins, termed CoAlation. Using anti...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/7/1362 |
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| author | Maria-Armineh Tossounian Maria Baczynska William Dalton Charlie Newell Yilin Ma Sayoni Das Jonathan Alexis Semelak Dario Ariel Estrin Valeriy Filonenko Madia Trujillo Sew Yeu Peak-Chew Mark Skehel Franca Fraternali Christine Orengo Ivan Gout |
| author_facet | Maria-Armineh Tossounian Maria Baczynska William Dalton Charlie Newell Yilin Ma Sayoni Das Jonathan Alexis Semelak Dario Ariel Estrin Valeriy Filonenko Madia Trujillo Sew Yeu Peak-Chew Mark Skehel Franca Fraternali Christine Orengo Ivan Gout |
| author_sort | Maria-Armineh Tossounian |
| collection | DOAJ |
| description | Coenzyme A (CoA) is a key cellular metabolite known for its diverse functions in metabolism and regulation of gene expression. CoA was recently shown to play an important antioxidant role under various cellular stress conditions by forming a disulfide bond with proteins, termed CoAlation. Using anti-CoA antibodies and liquid chromatography tandem mass spectrometry (LC-MS/MS) methodologies, CoAlated proteins were identified from various organisms/tissues/cell-lines under stress conditions. In this study, we integrated currently known CoAlated proteins into mammalian and bacterial datasets (CoAlomes), resulting in a total of 2093 CoAlated proteins (2862 CoAlation sites). Functional classification of these proteins showed that CoAlation is widespread among proteins involved in cellular metabolism, stress response and protein synthesis. Using 35 published CoAlated protein structures, we studied the stabilization interactions of each CoA segment (adenosine diphosphate (ADP) moiety and pantetheine tail) within the microenvironment of the modified cysteines. Alternating polar-non-polar residues, positively charged residues and hydrophobic interactions mainly stabilize the pantetheine tail, phosphate groups and the ADP moiety, respectively. A flexible nature of CoA is observed in examined structures, allowing it to adapt its conformation through interactions with residues surrounding the CoAlation site. Based on these findings, we propose three modes of CoA binding to proteins. Overall, this study summarizes currently available knowledge on CoAlated proteins, their functional distribution and CoA–protein stabilization interactions. |
| first_indexed | 2024-03-09T10:23:08Z |
| format | Article |
| id | doaj.art-56baf0cbdafb4d66a66c780f7cee1d2d |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T10:23:08Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-56baf0cbdafb4d66a66c780f7cee1d2d2023-12-01T21:50:02ZengMDPI AGAntioxidants2076-39212022-07-01117136210.3390/antiox11071362Profiling the Site of Protein CoAlation and Coenzyme A Stabilization InteractionsMaria-Armineh Tossounian0Maria Baczynska1William Dalton2Charlie Newell3Yilin Ma4Sayoni Das5Jonathan Alexis Semelak6Dario Ariel Estrin7Valeriy Filonenko8Madia Trujillo9Sew Yeu Peak-Chew10Mark Skehel11Franca Fraternali12Christine Orengo13Ivan Gout14Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartmento de Química Inorgánica Analítica y Química Física, INQUIMAE-CONICET, Universidad de Buenos Aires, Buenos Aires C1428EHA, ArgentinaDepartmento de Química Inorgánica Analítica y Química Física, INQUIMAE-CONICET, Universidad de Buenos Aires, Buenos Aires C1428EHA, ArgentinaInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03680 Kyiv, UkraineDepartamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo 11800, UruguayMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UKThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKRandall Centre for Cell and Molecular Biophysics, King’s College London, London WC2R 2LS, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKDepartment of Structural and Molecular Biology, University College London, London WC1E 6BT, UKCoenzyme A (CoA) is a key cellular metabolite known for its diverse functions in metabolism and regulation of gene expression. CoA was recently shown to play an important antioxidant role under various cellular stress conditions by forming a disulfide bond with proteins, termed CoAlation. Using anti-CoA antibodies and liquid chromatography tandem mass spectrometry (LC-MS/MS) methodologies, CoAlated proteins were identified from various organisms/tissues/cell-lines under stress conditions. In this study, we integrated currently known CoAlated proteins into mammalian and bacterial datasets (CoAlomes), resulting in a total of 2093 CoAlated proteins (2862 CoAlation sites). Functional classification of these proteins showed that CoAlation is widespread among proteins involved in cellular metabolism, stress response and protein synthesis. Using 35 published CoAlated protein structures, we studied the stabilization interactions of each CoA segment (adenosine diphosphate (ADP) moiety and pantetheine tail) within the microenvironment of the modified cysteines. Alternating polar-non-polar residues, positively charged residues and hydrophobic interactions mainly stabilize the pantetheine tail, phosphate groups and the ADP moiety, respectively. A flexible nature of CoA is observed in examined structures, allowing it to adapt its conformation through interactions with residues surrounding the CoAlation site. Based on these findings, we propose three modes of CoA binding to proteins. Overall, this study summarizes currently available knowledge on CoAlated proteins, their functional distribution and CoA–protein stabilization interactions.https://www.mdpi.com/2076-3921/11/7/1362coenzyme ACoAlationthiolationmixed-disulfideCoA stabilization interactionsoxidative stress |
| spellingShingle | Maria-Armineh Tossounian Maria Baczynska William Dalton Charlie Newell Yilin Ma Sayoni Das Jonathan Alexis Semelak Dario Ariel Estrin Valeriy Filonenko Madia Trujillo Sew Yeu Peak-Chew Mark Skehel Franca Fraternali Christine Orengo Ivan Gout Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions Antioxidants coenzyme A CoAlation thiolation mixed-disulfide CoA stabilization interactions oxidative stress |
| title | Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions |
| title_full | Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions |
| title_fullStr | Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions |
| title_full_unstemmed | Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions |
| title_short | Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions |
| title_sort | profiling the site of protein coalation and coenzyme a stabilization interactions |
| topic | coenzyme A CoAlation thiolation mixed-disulfide CoA stabilization interactions oxidative stress |
| url | https://www.mdpi.com/2076-3921/11/7/1362 |
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