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Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation
The Cytoplasmic Polyadenylation Element Binding proteins are RNA binding proteins involved in the translational regulation of mRNA. During cell cycle progression, CPEB1 is labeled for degradation by phosphorylation-dependent ubiquitination by the SCF(β−TrCP) ligase. The peptidyl-prolyl isomerase Pin...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601027/ https://www.ncbi.nlm.nih.gov/pubmed/26456073 http://dx.doi.org/10.1038/srep14990 |
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author | Schelhorn, Constanze Martín-Malpartida, Pau Suñol, David Macias, Maria J. |
author_facet | Schelhorn, Constanze Martín-Malpartida, Pau Suñol, David Macias, Maria J. |
author_sort | Schelhorn, Constanze |
collection | PubMed |
description | The Cytoplasmic Polyadenylation Element Binding proteins are RNA binding proteins involved in the translational regulation of mRNA. During cell cycle progression, CPEB1 is labeled for degradation by phosphorylation-dependent ubiquitination by the SCF(β−TrCP) ligase. The peptidyl-prolyl isomerase Pin1 plays a key role in CPEB1 degradation. Conditioned by the cell cycle stage, CPEB1 and Pin1 interactions occur in a phosphorylation-independent or -dependent manner. CPEB1 contains six potential phosphorylatable Pin1 binding sites. Using a set of biophysical techniques, we discovered that the pS210 site is unique, since it displays binding activity not only to the WW domain but also to the prolyl-isomerase domain of Pin1. The NMR structure of the Pin1 WW-CPEB1 pS210 (PDB ID: 2n1o) reveals that the pSerPro motif is bound in trans configuration through contacts with amino acids located in the first turn of the WW domain and the conserved tryptophan in the β3-strand. NMR relaxation analyses of Pin1 suggest that inter-domain flexibility is conferred by the modulation of the interaction with peptides containing the pS210 site, which is essential for degradation. |
format | Online Article Text |
id | pubmed-4601027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46010272015-10-21 Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation Schelhorn, Constanze Martín-Malpartida, Pau Suñol, David Macias, Maria J. Sci Rep Article The Cytoplasmic Polyadenylation Element Binding proteins are RNA binding proteins involved in the translational regulation of mRNA. During cell cycle progression, CPEB1 is labeled for degradation by phosphorylation-dependent ubiquitination by the SCF(β−TrCP) ligase. The peptidyl-prolyl isomerase Pin1 plays a key role in CPEB1 degradation. Conditioned by the cell cycle stage, CPEB1 and Pin1 interactions occur in a phosphorylation-independent or -dependent manner. CPEB1 contains six potential phosphorylatable Pin1 binding sites. Using a set of biophysical techniques, we discovered that the pS210 site is unique, since it displays binding activity not only to the WW domain but also to the prolyl-isomerase domain of Pin1. The NMR structure of the Pin1 WW-CPEB1 pS210 (PDB ID: 2n1o) reveals that the pSerPro motif is bound in trans configuration through contacts with amino acids located in the first turn of the WW domain and the conserved tryptophan in the β3-strand. NMR relaxation analyses of Pin1 suggest that inter-domain flexibility is conferred by the modulation of the interaction with peptides containing the pS210 site, which is essential for degradation. Nature Publishing Group 2015-10-12 /pmc/articles/PMC4601027/ /pubmed/26456073 http://dx.doi.org/10.1038/srep14990 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Schelhorn, Constanze Martín-Malpartida, Pau Suñol, David Macias, Maria J. Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation |
title | Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation |
title_full | Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation |
title_fullStr | Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation |
title_full_unstemmed | Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation |
title_short | Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation |
title_sort | structural analysis of the pin1-cpeb1 interaction and its potential role in cpeb1 degradation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601027/ https://www.ncbi.nlm.nih.gov/pubmed/26456073 http://dx.doi.org/10.1038/srep14990 |
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