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Mapping the allosteric network within a SH3 domain

SH3 domains are very abundant protein-protein interactions modules, involved in the regulation of several cellular processes. Whilst they have been associated to allosteric communication pathways between contiguous domains in multi-domain proteins, there is lack of information regarding the intra-do...

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Autores principales: Malagrinò, Francesca, Troilo, Francesca, Bonetti, Daniela, Toto, Angelo, Gianni, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547694/
https://www.ncbi.nlm.nih.gov/pubmed/31164678
http://dx.doi.org/10.1038/s41598-019-44656-8
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author Malagrinò, Francesca
Troilo, Francesca
Bonetti, Daniela
Toto, Angelo
Gianni, Stefano
author_facet Malagrinò, Francesca
Troilo, Francesca
Bonetti, Daniela
Toto, Angelo
Gianni, Stefano
author_sort Malagrinò, Francesca
collection PubMed
description SH3 domains are very abundant protein-protein interactions modules, involved in the regulation of several cellular processes. Whilst they have been associated to allosteric communication pathways between contiguous domains in multi-domain proteins, there is lack of information regarding the intra-domain allosteric cross-talk within the SH3 moiety. Here we scrutinize the presence of an allosteric network in the C-terminal SH3 domain of Grb2 protein, upon binding the Grb2-associated binding 2 protein. To explore allostery, we performed double mutant cycle analysis, a powerful quantitative approach based on mutagenesis in conjunction with kinetic experiments. Data reveal the presence of an unexpected allosteric sparse network that modulates the affinity between the SH3 domain and its physiological partner.
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spelling pubmed-65476942019-06-10 Mapping the allosteric network within a SH3 domain Malagrinò, Francesca Troilo, Francesca Bonetti, Daniela Toto, Angelo Gianni, Stefano Sci Rep Article SH3 domains are very abundant protein-protein interactions modules, involved in the regulation of several cellular processes. Whilst they have been associated to allosteric communication pathways between contiguous domains in multi-domain proteins, there is lack of information regarding the intra-domain allosteric cross-talk within the SH3 moiety. Here we scrutinize the presence of an allosteric network in the C-terminal SH3 domain of Grb2 protein, upon binding the Grb2-associated binding 2 protein. To explore allostery, we performed double mutant cycle analysis, a powerful quantitative approach based on mutagenesis in conjunction with kinetic experiments. Data reveal the presence of an unexpected allosteric sparse network that modulates the affinity between the SH3 domain and its physiological partner. Nature Publishing Group UK 2019-06-04 /pmc/articles/PMC6547694/ /pubmed/31164678 http://dx.doi.org/10.1038/s41598-019-44656-8 Text en © The Author(s) 2019 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/.
spellingShingle Article
Malagrinò, Francesca
Troilo, Francesca
Bonetti, Daniela
Toto, Angelo
Gianni, Stefano
Mapping the allosteric network within a SH3 domain
title Mapping the allosteric network within a SH3 domain
title_full Mapping the allosteric network within a SH3 domain
title_fullStr Mapping the allosteric network within a SH3 domain
title_full_unstemmed Mapping the allosteric network within a SH3 domain
title_short Mapping the allosteric network within a SH3 domain
title_sort mapping the allosteric network within a sh3 domain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547694/
https://www.ncbi.nlm.nih.gov/pubmed/31164678
http://dx.doi.org/10.1038/s41598-019-44656-8
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