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The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85

SH2 domains are protein domains that modulate protein–protein interactions through a specific interaction with sequences containing phosphorylated tyrosines. In this work, we analyze the folding pathway of the C-terminal SH2 domain of the p85 regulatory subunit of the protein PI3K, which presents a...

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Autores principales: Troilo, Francesca, Malagrinò, Francesca, Visconti, Lorenzo, Toto, Angelo, Gianni, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982175/
https://www.ncbi.nlm.nih.gov/pubmed/31878075
http://dx.doi.org/10.3390/ijms21010125
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author Troilo, Francesca
Malagrinò, Francesca
Visconti, Lorenzo
Toto, Angelo
Gianni, Stefano
author_facet Troilo, Francesca
Malagrinò, Francesca
Visconti, Lorenzo
Toto, Angelo
Gianni, Stefano
author_sort Troilo, Francesca
collection PubMed
description SH2 domains are protein domains that modulate protein–protein interactions through a specific interaction with sequences containing phosphorylated tyrosines. In this work, we analyze the folding pathway of the C-terminal SH2 domain of the p85 regulatory subunit of the protein PI3K, which presents a proline residue in a cis configuration in the loop between the βE and βF strands. By employing single and double jump folding and unfolding experiments, we demonstrate the presence of an on-pathway intermediate that transiently accumulates during (un)folding. By comparing the kinetics of folding of the wild-type protein to that of a site-directed variant of C-SH2 in which the proline was replaced with an alanine, we demonstrate that this intermediate is dictated by the peptidyl prolyl cis-trans isomerization. The results are discussed in the light of previous work on the effect of peptidyl prolyl cis-trans isomerization on folding events.
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spelling pubmed-69821752020-02-07 The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85 Troilo, Francesca Malagrinò, Francesca Visconti, Lorenzo Toto, Angelo Gianni, Stefano Int J Mol Sci Article SH2 domains are protein domains that modulate protein–protein interactions through a specific interaction with sequences containing phosphorylated tyrosines. In this work, we analyze the folding pathway of the C-terminal SH2 domain of the p85 regulatory subunit of the protein PI3K, which presents a proline residue in a cis configuration in the loop between the βE and βF strands. By employing single and double jump folding and unfolding experiments, we demonstrate the presence of an on-pathway intermediate that transiently accumulates during (un)folding. By comparing the kinetics of folding of the wild-type protein to that of a site-directed variant of C-SH2 in which the proline was replaced with an alanine, we demonstrate that this intermediate is dictated by the peptidyl prolyl cis-trans isomerization. The results are discussed in the light of previous work on the effect of peptidyl prolyl cis-trans isomerization on folding events. MDPI 2019-12-23 /pmc/articles/PMC6982175/ /pubmed/31878075 http://dx.doi.org/10.3390/ijms21010125 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Troilo, Francesca
Malagrinò, Francesca
Visconti, Lorenzo
Toto, Angelo
Gianni, Stefano
The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85
title The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85
title_full The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85
title_fullStr The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85
title_full_unstemmed The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85
title_short The Effect of Proline cis-trans Isomerization on the Folding of the C-Terminal SH2 Domain from p85
title_sort effect of proline cis-trans isomerization on the folding of the c-terminal sh2 domain from p85
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982175/
https://www.ncbi.nlm.nih.gov/pubmed/31878075
http://dx.doi.org/10.3390/ijms21010125
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