Cargando…
Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin
Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151440/ https://www.ncbi.nlm.nih.gov/pubmed/28846639 http://dx.doi.org/10.3390/molecules22091414 |
_version_ | 1783357153925398528 |
---|---|
author | Kitazawa, Soichiro Yagi-Utsumi, Maho Kato, Koichi Kitahara, Ryo |
author_facet | Kitazawa, Soichiro Yagi-Utsumi, Maho Kato, Koichi Kitahara, Ryo |
author_sort | Kitazawa, Soichiro |
collection | PubMed |
description | Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the salt bridge between K11 and E34 and the hydrogen bond between I36 and Q41, which are predicted to control the fluctuation between the basic folded state, N(1), and the alternatively folded state, N(2), of the protein, using high-pressure NMR spectroscopy. The E34A mutation, which disrupts the salt bridge, did not alter picosecond–to–nanosecond, microsecond–to–millisecond dynamic motions, and stability of the protein, while the Q41N mutation, which destabilizes the hydrogen bond, specifically amplified the N(1)–N(2) conformational fluctuation and decreased stability. Based on the observed thermodynamic stabilities of the various conformational states, we showed that in the Q41N mutant, the N(1) state is more significantly destabilized than the N(2) state, resulting in an increase in the relative population of N(2). Identifying the interactions controlling specific motions of a protein will facilitate molecular design to achieve functional dynamics beyond native state dynamics. |
format | Online Article Text |
id | pubmed-6151440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61514402018-11-13 Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin Kitazawa, Soichiro Yagi-Utsumi, Maho Kato, Koichi Kitahara, Ryo Molecules Article Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the salt bridge between K11 and E34 and the hydrogen bond between I36 and Q41, which are predicted to control the fluctuation between the basic folded state, N(1), and the alternatively folded state, N(2), of the protein, using high-pressure NMR spectroscopy. The E34A mutation, which disrupts the salt bridge, did not alter picosecond–to–nanosecond, microsecond–to–millisecond dynamic motions, and stability of the protein, while the Q41N mutation, which destabilizes the hydrogen bond, specifically amplified the N(1)–N(2) conformational fluctuation and decreased stability. Based on the observed thermodynamic stabilities of the various conformational states, we showed that in the Q41N mutant, the N(1) state is more significantly destabilized than the N(2) state, resulting in an increase in the relative population of N(2). Identifying the interactions controlling specific motions of a protein will facilitate molecular design to achieve functional dynamics beyond native state dynamics. MDPI 2017-08-28 /pmc/articles/PMC6151440/ /pubmed/28846639 http://dx.doi.org/10.3390/molecules22091414 Text en © 2017 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 Kitazawa, Soichiro Yagi-Utsumi, Maho Kato, Koichi Kitahara, Ryo Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin |
title | Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin |
title_full | Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin |
title_fullStr | Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin |
title_full_unstemmed | Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin |
title_short | Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin |
title_sort | interactions controlling the slow dynamic conformational motions of ubiquitin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151440/ https://www.ncbi.nlm.nih.gov/pubmed/28846639 http://dx.doi.org/10.3390/molecules22091414 |
work_keys_str_mv | AT kitazawasoichiro interactionscontrollingtheslowdynamicconformationalmotionsofubiquitin AT yagiutsumimaho interactionscontrollingtheslowdynamicconformationalmotionsofubiquitin AT katokoichi interactionscontrollingtheslowdynamicconformationalmotionsofubiquitin AT kitahararyo interactionscontrollingtheslowdynamicconformationalmotionsofubiquitin |