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How phosphorylation impacts intrinsically disordered proteins and their function

Phosphorylation is the most common post-translational modification (PTM) in eukaryotes, occurring particularly frequently in intrinsically disordered proteins (IDPs). These proteins are highly flexible and dynamic by nature. Thus, it is intriguing that the addition of a single phosphoryl group to a...

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Autores principales: Newcombe, Estella A., Delaforge, Elise, Hartmann-Petersen, Rasmus, Skriver, Karen, Kragelund, Birthe B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760426/
https://www.ncbi.nlm.nih.gov/pubmed/36350035
http://dx.doi.org/10.1042/EBC20220060
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author Newcombe, Estella A.
Delaforge, Elise
Hartmann-Petersen, Rasmus
Skriver, Karen
Kragelund, Birthe B.
author_facet Newcombe, Estella A.
Delaforge, Elise
Hartmann-Petersen, Rasmus
Skriver, Karen
Kragelund, Birthe B.
author_sort Newcombe, Estella A.
collection PubMed
description Phosphorylation is the most common post-translational modification (PTM) in eukaryotes, occurring particularly frequently in intrinsically disordered proteins (IDPs). These proteins are highly flexible and dynamic by nature. Thus, it is intriguing that the addition of a single phosphoryl group to a disordered chain can impact its function so dramatically. Furthermore, as many IDPs carry multiple phosphorylation sites, the number of possible states increases, enabling larger complexities and novel mechanisms. Although a chemically simple and well-understood process, the impact of phosphorylation on the conformational ensemble and molecular function of IDPs, not to mention biological output, is highly complex and diverse. Since the discovery of the first phosphorylation site in proteins 75 years ago, we have come to a much better understanding of how this PTM works, but with the diversity of IDPs and their capacity for carrying multiple phosphoryl groups, the complexity grows. In this Essay, we highlight some of the basic effects of IDP phosphorylation, allowing it to serve as starting point when embarking on studies into this topic. We further describe how recent complex cases of multisite phosphorylation of IDPs have been instrumental in widening our view on the effect of protein phosphorylation. Finally, we put forward perspectives on the phosphorylation of IDPs, both in relation to disease and in context of other PTMs; areas where deep insight remains to be uncovered.
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spelling pubmed-97604262022-12-23 How phosphorylation impacts intrinsically disordered proteins and their function Newcombe, Estella A. Delaforge, Elise Hartmann-Petersen, Rasmus Skriver, Karen Kragelund, Birthe B. Essays Biochem Biophysics Phosphorylation is the most common post-translational modification (PTM) in eukaryotes, occurring particularly frequently in intrinsically disordered proteins (IDPs). These proteins are highly flexible and dynamic by nature. Thus, it is intriguing that the addition of a single phosphoryl group to a disordered chain can impact its function so dramatically. Furthermore, as many IDPs carry multiple phosphorylation sites, the number of possible states increases, enabling larger complexities and novel mechanisms. Although a chemically simple and well-understood process, the impact of phosphorylation on the conformational ensemble and molecular function of IDPs, not to mention biological output, is highly complex and diverse. Since the discovery of the first phosphorylation site in proteins 75 years ago, we have come to a much better understanding of how this PTM works, but with the diversity of IDPs and their capacity for carrying multiple phosphoryl groups, the complexity grows. In this Essay, we highlight some of the basic effects of IDP phosphorylation, allowing it to serve as starting point when embarking on studies into this topic. We further describe how recent complex cases of multisite phosphorylation of IDPs have been instrumental in widening our view on the effect of protein phosphorylation. Finally, we put forward perspectives on the phosphorylation of IDPs, both in relation to disease and in context of other PTMs; areas where deep insight remains to be uncovered. Portland Press Ltd. 2022-12 2022-12-16 /pmc/articles/PMC9760426/ /pubmed/36350035 http://dx.doi.org/10.1042/EBC20220060 Text en © 2022 The Author(s). https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . Open access for this article was enabled by the participation of University of Cambridge in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC.
spellingShingle Biophysics
Newcombe, Estella A.
Delaforge, Elise
Hartmann-Petersen, Rasmus
Skriver, Karen
Kragelund, Birthe B.
How phosphorylation impacts intrinsically disordered proteins and their function
title How phosphorylation impacts intrinsically disordered proteins and their function
title_full How phosphorylation impacts intrinsically disordered proteins and their function
title_fullStr How phosphorylation impacts intrinsically disordered proteins and their function
title_full_unstemmed How phosphorylation impacts intrinsically disordered proteins and their function
title_short How phosphorylation impacts intrinsically disordered proteins and their function
title_sort how phosphorylation impacts intrinsically disordered proteins and their function
topic Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760426/
https://www.ncbi.nlm.nih.gov/pubmed/36350035
http://dx.doi.org/10.1042/EBC20220060
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