Cellular ATP levels determine the stability of a nucleotide kinase
- The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3'-phosphoadenosine-5'-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from \(\Delta G_{f}^{0}\) = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.
| Author: | Oliver BrylskiGND, Puja ShresthaGND, Patricia GnuttGND, David GnuttGND, Jonathan Wolf MüllerGND, Simon EbbinghausORCiDGND |
|---|---|
| URN: | urn:nbn:de:hbz:294-87279 |
| DOI: | https://doi.org/10.3389/fmolb.2021.790304 |
| Parent Title (English): | Frontiers in molecular biosciences |
| Publisher: | Frontiers |
| Place of publication: | Lausanne |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 2022/03/16 |
| Date of first Publication: | 2021/12/13 |
| Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
| Tag: | ATP depletion; PAPS synthase; alanine scanning; cellular stress; in-cell spectroscopy; ligand binding; protein folding stability; sulfation pathways |
| Volume: | 8 |
| Issue: | Article 790304 |
| First Page: | 790304-1 |
| Last Page: | 790304-12 |
| Institutes/Facilities: | Lehrstuhl für Physikalische Chemie II |
| Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Chemie, Kristallographie, Mineralogie |
| open_access (DINI-Set): | open_access |
| faculties: | Fakultät für Chemie und Biochemie |
| Licence (English): |  Creative Commons - CC BY 4.0 - Attribution 4.0 International |
