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Structural and functional consequences of NEDD8 phosphorylation
Ubiquitin (Ub) and Ub-like proteins (Ubls) such as NEDD8 are best known for their function as covalent modifiers of other proteins but they are also themselves subject to post-translational modifications including phosphorylation. While functions of phosphorylated Ub (pUb) have been characterized, t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020517/ https://www.ncbi.nlm.nih.gov/pubmed/34642328 http://dx.doi.org/10.1038/s41467-021-26189-9 |
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author | Stuber, Katrin Schneider, Tobias Werner, Jill Kovermann, Michael Marx, Andreas Scheffner, Martin |
author_facet | Stuber, Katrin Schneider, Tobias Werner, Jill Kovermann, Michael Marx, Andreas Scheffner, Martin |
author_sort | Stuber, Katrin |
collection | PubMed |
description | Ubiquitin (Ub) and Ub-like proteins (Ubls) such as NEDD8 are best known for their function as covalent modifiers of other proteins but they are also themselves subject to post-translational modifications including phosphorylation. While functions of phosphorylated Ub (pUb) have been characterized, the consequences of Ubl phosphorylation remain unclear. Here we report that NEDD8 can be phosphorylated at S65 - the same site as Ub - and that S65 phosphorylation affects the structural dynamics of NEDD8 and Ub in a similar manner. While both pUb and phosphorylated NEDD8 (pNEDD8) can allosterically activate the Ub ligase Parkin, they have different protein interactomes that in turn are distinct from those of unmodified Ub and NEDD8. Among the preferential pNEDD8 interactors are HSP70 family members and we show that pNEDD8 stimulates HSP70 ATPase activity more pronouncedly than unmodified NEDD8. Our findings highlight the general importance of Ub/NEDD8 phosphorylation and support the notion that the function of pUb/pNEDD8 does not require their covalent attachment to other proteins. |
format | Online Article Text |
id | pubmed-9020517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90205172022-04-20 Structural and functional consequences of NEDD8 phosphorylation Stuber, Katrin Schneider, Tobias Werner, Jill Kovermann, Michael Marx, Andreas Scheffner, Martin Nat Commun Article Ubiquitin (Ub) and Ub-like proteins (Ubls) such as NEDD8 are best known for their function as covalent modifiers of other proteins but they are also themselves subject to post-translational modifications including phosphorylation. While functions of phosphorylated Ub (pUb) have been characterized, the consequences of Ubl phosphorylation remain unclear. Here we report that NEDD8 can be phosphorylated at S65 - the same site as Ub - and that S65 phosphorylation affects the structural dynamics of NEDD8 and Ub in a similar manner. While both pUb and phosphorylated NEDD8 (pNEDD8) can allosterically activate the Ub ligase Parkin, they have different protein interactomes that in turn are distinct from those of unmodified Ub and NEDD8. Among the preferential pNEDD8 interactors are HSP70 family members and we show that pNEDD8 stimulates HSP70 ATPase activity more pronouncedly than unmodified NEDD8. Our findings highlight the general importance of Ub/NEDD8 phosphorylation and support the notion that the function of pUb/pNEDD8 does not require their covalent attachment to other proteins. Nature Publishing Group UK 2021-10-12 /pmc/articles/PMC9020517/ /pubmed/34642328 http://dx.doi.org/10.1038/s41467-021-26189-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Stuber, Katrin Schneider, Tobias Werner, Jill Kovermann, Michael Marx, Andreas Scheffner, Martin Structural and functional consequences of NEDD8 phosphorylation |
title | Structural and functional consequences of NEDD8 phosphorylation |
title_full | Structural and functional consequences of NEDD8 phosphorylation |
title_fullStr | Structural and functional consequences of NEDD8 phosphorylation |
title_full_unstemmed | Structural and functional consequences of NEDD8 phosphorylation |
title_short | Structural and functional consequences of NEDD8 phosphorylation |
title_sort | structural and functional consequences of nedd8 phosphorylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020517/ https://www.ncbi.nlm.nih.gov/pubmed/34642328 http://dx.doi.org/10.1038/s41467-021-26189-9 |
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