دورية أكاديمية
A palmitoyl transferase chemical–genetic system to map ZDHHC-specific S-acylation
| العنوان: | A palmitoyl transferase chemical–genetic system to map ZDHHC-specific S-acylation |
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| المؤلفون: | Ocasio, Cory A., Baggelaar, Marc P., Sipthorp, James, Losada de la Lastra, Ana, Tavares, Manuel, Volarić, Jana, Soudy, Christelle, Storck, Elisabeth M., Houghton, Jack W., Palma-Duran, Susana A., MacRae, James I., Tomić, Goran, Carr, Lotte, Downward, Julian, Eggert, Ulrike S., Tate, Edward W. |
| المساهمون: | Cancer Research UK, Wellcome Trust, European Research Council Advanced Grant RASImmune, RCUK | Engineering and Physical Sciences Research Council |
| المصدر: | Nature Biotechnology ; ISSN 1087-0156 1546-1696 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biomedical Engineering, Molecular Medicine, Applied Microbiology and Biotechnology, Bioengineering, Biotechnology |
| الوصف: | The 23 human zinc finger Asp-His-His-Cys motif-containing (ZDHHC) S -acyltransferases catalyze long-chain S -acylation at cysteine residues across an extensive network of hundreds of proteins important for normal physiology or dysregulated in disease. Here we present a technology to directly map the protein substrates of a specific ZDHHC at the whole-proteome level, in intact cells. Structure-guided engineering of paired ZDHHC ‘hole’ mutants and ‘bumped’ chemically tagged fatty acid probes enabled probe transfer to specific protein substrates with excellent selectivity over wild-type ZDHHCs. Chemical–genetic systems were exemplified for five human ZDHHCs (3, 7, 11, 15 and 20) and applied to generate de novo ZDHHC substrate profiles, identifying >300 substrates and S -acylation sites for new functionally diverse proteins across multiple cell lines. We expect that this platform will elucidate S -acylation biology for a wide range of models and organisms. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41587-023-02030-0 |
| الإتاحة: | https://doi.org/10.1038/s41587-023-02030-0Test https://www.nature.com/articles/s41587-023-02030-0.pdfTest https://www.nature.com/articles/s41587-023-02030-0Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.A391E25C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41587-023-02030-0 |
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