Tossounian, Maria-Armineh;
Baczynska, Maria;
Dalton, William;
Newell, Charlie;
Ma, Yilin;
Das, Sayoni;
Semelak, Jonathan Alexis;
... Gout, Ivan; + view all
(2022)
Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions.
Antioxidants
, 11
(7)
, Article 1362. 10.3390/antiox11071362.
Preview |
Text
antioxidants-11-01362-v2.pdf - Published Version Download (2MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/antiox11071362 |
| Publisher version: | https://doi.org/10.3390/antiox11071362 |
| Language: | English |
| Additional information: | This is an open access article distributed under 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. |
| Keywords: | coenzyme A; CoAlation; thiolation; mixed-disulfide; CoA stabilization interactions; oxidative stress |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10152726 |
Archive Staff Only
 |
View Item |
