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Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume

Molecular dynamics simulations are used to explore the effects of chaperonin-like cages on knotted proteins with very low sequence similarity, different depths of a knot but with a similar fold, and the same type of topology. The investigated proteins are VirC2, DndE and MJ0366 with two depths of a...

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Autores principales: Niewieczerzal, Szymon, Sulkowska, Joanna I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425179/
https://www.ncbi.nlm.nih.gov/pubmed/28489858
http://dx.doi.org/10.1371/journal.pone.0176744
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author Niewieczerzal, Szymon
Sulkowska, Joanna I.
author_facet Niewieczerzal, Szymon
Sulkowska, Joanna I.
author_sort Niewieczerzal, Szymon
collection PubMed
description Molecular dynamics simulations are used to explore the effects of chaperonin-like cages on knotted proteins with very low sequence similarity, different depths of a knot but with a similar fold, and the same type of topology. The investigated proteins are VirC2, DndE and MJ0366 with two depths of a knot. A comprehensive picture how encapsulation influences folding rates is provided based on the analysis of different cage sizes and temperature conditions. Neither of these two effects with regard to knotted proteins has been studied by means of molecular dynamics simulations with coarse-grained structure-based models before. We show that encapsulation in a chaperonin is sufficient to self-tie and untie small knotted proteins (VirC2, DndE), for which the equilibrium process is not accessible in the bulk solvent. Furthermore, we find that encapsulation reduces backtracking that arises from the destabilisation of nucleation sites, smoothing the free energy landscape. However, this effect can also be coupled with temperature rise. Encapsulation facilitates knotting at the early stage of folding and can enhance an alternative folding route. Comparison to unknotted proteins with the same fold shows directly how encapsulation influences the free energy landscape. In addition, we find that as the size of the cage decreases, folding times increase almost exponentially in a certain range of cage sizes, in accordance with confinement theory and experimental data for unknotted proteins.
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spelling pubmed-54251792017-05-15 Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume Niewieczerzal, Szymon Sulkowska, Joanna I. PLoS One Research Article Molecular dynamics simulations are used to explore the effects of chaperonin-like cages on knotted proteins with very low sequence similarity, different depths of a knot but with a similar fold, and the same type of topology. The investigated proteins are VirC2, DndE and MJ0366 with two depths of a knot. A comprehensive picture how encapsulation influences folding rates is provided based on the analysis of different cage sizes and temperature conditions. Neither of these two effects with regard to knotted proteins has been studied by means of molecular dynamics simulations with coarse-grained structure-based models before. We show that encapsulation in a chaperonin is sufficient to self-tie and untie small knotted proteins (VirC2, DndE), for which the equilibrium process is not accessible in the bulk solvent. Furthermore, we find that encapsulation reduces backtracking that arises from the destabilisation of nucleation sites, smoothing the free energy landscape. However, this effect can also be coupled with temperature rise. Encapsulation facilitates knotting at the early stage of folding and can enhance an alternative folding route. Comparison to unknotted proteins with the same fold shows directly how encapsulation influences the free energy landscape. In addition, we find that as the size of the cage decreases, folding times increase almost exponentially in a certain range of cage sizes, in accordance with confinement theory and experimental data for unknotted proteins. Public Library of Science 2017-05-10 /pmc/articles/PMC5425179/ /pubmed/28489858 http://dx.doi.org/10.1371/journal.pone.0176744 Text en © 2017 Niewieczerzal, Sulkowska http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Niewieczerzal, Szymon
Sulkowska, Joanna I.
Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume
title Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume
title_full Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume
title_fullStr Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume
title_full_unstemmed Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume
title_short Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume
title_sort knotting and unknotting proteins in the chaperonin cage: effects of the excluded volume
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425179/
https://www.ncbi.nlm.nih.gov/pubmed/28489858
http://dx.doi.org/10.1371/journal.pone.0176744
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