Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1783491254921723904 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6982175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT troilofrancesca theeffectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT malagrinofrancesca theeffectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT viscontilorenzo theeffectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT totoangelo theeffectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT giannistefano theeffectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT troilofrancesca effectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT malagrinofrancesca effectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT viscontilorenzo effectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT totoangelo effectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 AT giannistefano effectofprolinecistransisomerizationonthefoldingofthecterminalsh2domainfromp85 |