Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae
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Protein N-terminal (Nt) acetylation is one of the most abundant modifications in eukaryotes, covering ~50-80 % of the proteome, depending on species. Cells with defective Nt-acetylation display a wide array of phenotypes such as impaired growth, mating defects and increased stress sensitivity. However, the pleiotropic nature of these effects has hampered our understanding of the functional impact of protein Nt-acetylation. The main enzyme responsible for Nt-acetylation throughout the eukaryotic kingdom is the N-terminal acetyltransferase NatA. Here we employ a multi-dimensional proteomics approach to analyze Saccharomyces cerevisiae lacking NatA activity, which causes global proteome remodeling. Pulsed-SILAC experiments reveals that NatA-deficient strains consistently increase degradation of ribosomal proteins compared to wild type. Explaining this phenomenon, thermal proteome profiling uncovers decreased thermostability of ribosomes in NatA-knockouts. Our data are in agreement with a role for Nt-acetylation in promoting stability for parts of the proteome by enhancing the avidity of protein-protein interactions and folding.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 4517 |
| Tidsskrift | Nature Communications |
| Vol/bind | 14 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
Work at the Novo Nordisk Foundation Center for Protein Research is funded in part by a generous donation from the Novo Nordisk Foundation (grant NNF14CC0001) and the European Union’s Horizon 2020 research and innovation program (grant EPIC-XS-823839). U.H.G. was supported by the Novo Nordisk Foundation’s Copenhagen Bioscience PhD Program (grant NNF16CC0020906). This work was supported by grants from the Swedish Research Council (Grant 2021-04655 to M.E.J.), the Norwegian Health Authorities of Western Norway (F-12540 to T.A.), the Norwegian Cancer Society (171752-PR-2009-0222 to T.A.), the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (Grant 772039 to T.A.). The flow cytometry analysis was performed at the Flow Cytometry Core Facility, Department of Clinical Science, University of Bergen, Norway.
Funding Information:
Work at the Novo Nordisk Foundation Center for Protein Research is funded in part by a generous donation from the Novo Nordisk Foundation (grant NNF14CC0001) and the European Union’s Horizon 2020 research and innovation program (grant EPIC-XS-823839). U.H.G. was supported by the Novo Nordisk Foundation’s Copenhagen Bioscience PhD Program (grant NNF16CC0020906). This work was supported by grants from the Swedish Research Council (Grant 2021-04655 to M.E.J.), the Norwegian Health Authorities of Western Norway (F-12540 to T.A.), the Norwegian Cancer Society (171752-PR-2009-0222 to T.A.), the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (Grant 772039 to T.A.). The flow cytometry analysis was performed at the Flow Cytometry Core Facility, Department of Clinical Science, University of Bergen, Norway.
Publisher Copyright:
© 2023, The Author(s).
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