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Molecular architecture of the glycogen- committed PP1/PTG holoenzyme
The delicate alternation between glycogen synthesis and degradation is governed by the interplay between key regulatory enzymes altering the activity of glycogen synthase and phosphorylase. Among these, the PP1 phosphatase promotes glycogenesis while inhibiting glycogenolysis. PP1 is, however, a mas...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582199/ https://www.ncbi.nlm.nih.gov/pubmed/36261419 http://dx.doi.org/10.1038/s41467-022-33693-z |
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author | Semrau, Marta Stefania Giachin, Gabriele Covaceuszach, Sonia Cassetta, Alberto Demitri, Nicola Storici, Paola Lolli, Graziano |
author_facet | Semrau, Marta Stefania Giachin, Gabriele Covaceuszach, Sonia Cassetta, Alberto Demitri, Nicola Storici, Paola Lolli, Graziano |
author_sort | Semrau, Marta Stefania |
collection | PubMed |
description | The delicate alternation between glycogen synthesis and degradation is governed by the interplay between key regulatory enzymes altering the activity of glycogen synthase and phosphorylase. Among these, the PP1 phosphatase promotes glycogenesis while inhibiting glycogenolysis. PP1 is, however, a master regulator of a variety of cellular processes, being conveniently directed to each of them by scaffolding subunits. PTG, Protein Targeting to Glycogen, addresses PP1 action to glycogen granules. In Lafora disease, the most aggressive pediatric epilepsy, genetic alterations leading to PTG accumulation cause the deposition of insoluble polyglucosans in neurons. Here, we report the crystallographic structure of the ternary complex PP1/PTG/carbohydrate. We further refine the mechanism of the PTG-mediated PP1 recruitment to glycogen by identifying i) an unusual combination of recruitment sites, ii) their contributions to the overall binding affinity, and iii) the conformational heterogeneity of this complex by in solution SAXS analyses. |
format | Online Article Text |
id | pubmed-9582199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95821992022-10-21 Molecular architecture of the glycogen- committed PP1/PTG holoenzyme Semrau, Marta Stefania Giachin, Gabriele Covaceuszach, Sonia Cassetta, Alberto Demitri, Nicola Storici, Paola Lolli, Graziano Nat Commun Article The delicate alternation between glycogen synthesis and degradation is governed by the interplay between key regulatory enzymes altering the activity of glycogen synthase and phosphorylase. Among these, the PP1 phosphatase promotes glycogenesis while inhibiting glycogenolysis. PP1 is, however, a master regulator of a variety of cellular processes, being conveniently directed to each of them by scaffolding subunits. PTG, Protein Targeting to Glycogen, addresses PP1 action to glycogen granules. In Lafora disease, the most aggressive pediatric epilepsy, genetic alterations leading to PTG accumulation cause the deposition of insoluble polyglucosans in neurons. Here, we report the crystallographic structure of the ternary complex PP1/PTG/carbohydrate. We further refine the mechanism of the PTG-mediated PP1 recruitment to glycogen by identifying i) an unusual combination of recruitment sites, ii) their contributions to the overall binding affinity, and iii) the conformational heterogeneity of this complex by in solution SAXS analyses. Nature Publishing Group UK 2022-10-19 /pmc/articles/PMC9582199/ /pubmed/36261419 http://dx.doi.org/10.1038/s41467-022-33693-z Text en © The Author(s) 2022 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 Semrau, Marta Stefania Giachin, Gabriele Covaceuszach, Sonia Cassetta, Alberto Demitri, Nicola Storici, Paola Lolli, Graziano Molecular architecture of the glycogen- committed PP1/PTG holoenzyme |
title | Molecular architecture of the glycogen- committed PP1/PTG holoenzyme |
title_full | Molecular architecture of the glycogen- committed PP1/PTG holoenzyme |
title_fullStr | Molecular architecture of the glycogen- committed PP1/PTG holoenzyme |
title_full_unstemmed | Molecular architecture of the glycogen- committed PP1/PTG holoenzyme |
title_short | Molecular architecture of the glycogen- committed PP1/PTG holoenzyme |
title_sort | molecular architecture of the glycogen- committed pp1/ptg holoenzyme |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582199/ https://www.ncbi.nlm.nih.gov/pubmed/36261419 http://dx.doi.org/10.1038/s41467-022-33693-z |
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