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Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation
Identifying the forces that drive proteins to misfold and aggregate, rather than to fold into their functional states, is fundamental to our understanding of living systems and to our ability to combat protein deposition disorders such as Alzheimer's disease and the spongiform encephalopathies....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192805/ https://www.ncbi.nlm.nih.gov/pubmed/22022239 http://dx.doi.org/10.1371/journal.pcbi.1002169 |
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author | Fitzpatrick, Anthony W. Knowles, Tuomas P. J. Waudby, Christopher A. Vendruscolo, Michele Dobson, Christopher M. |
author_facet | Fitzpatrick, Anthony W. Knowles, Tuomas P. J. Waudby, Christopher A. Vendruscolo, Michele Dobson, Christopher M. |
author_sort | Fitzpatrick, Anthony W. |
collection | PubMed |
description | Identifying the forces that drive proteins to misfold and aggregate, rather than to fold into their functional states, is fundamental to our understanding of living systems and to our ability to combat protein deposition disorders such as Alzheimer's disease and the spongiform encephalopathies. We report here the finding that the balance between hydrophobic and hydrogen bonding interactions is different for proteins in the processes of folding to their native states and misfolding to the alternative amyloid structures. We find that the minima of the protein free energy landscape for folding and misfolding tend to be respectively dominated by hydrophobic and by hydrogen bonding interactions. These results characterise the nature of the interactions that determine the competition between folding and misfolding of proteins by revealing that the stability of native proteins is primarily determined by hydrophobic interactions between side-chains, while the stability of amyloid fibrils depends more on backbone intermolecular hydrogen bonding interactions. |
format | Online Article Text |
id | pubmed-3192805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31928052011-10-21 Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation Fitzpatrick, Anthony W. Knowles, Tuomas P. J. Waudby, Christopher A. Vendruscolo, Michele Dobson, Christopher M. PLoS Comput Biol Research Article Identifying the forces that drive proteins to misfold and aggregate, rather than to fold into their functional states, is fundamental to our understanding of living systems and to our ability to combat protein deposition disorders such as Alzheimer's disease and the spongiform encephalopathies. We report here the finding that the balance between hydrophobic and hydrogen bonding interactions is different for proteins in the processes of folding to their native states and misfolding to the alternative amyloid structures. We find that the minima of the protein free energy landscape for folding and misfolding tend to be respectively dominated by hydrophobic and by hydrogen bonding interactions. These results characterise the nature of the interactions that determine the competition between folding and misfolding of proteins by revealing that the stability of native proteins is primarily determined by hydrophobic interactions between side-chains, while the stability of amyloid fibrils depends more on backbone intermolecular hydrogen bonding interactions. Public Library of Science 2011-10-13 /pmc/articles/PMC3192805/ /pubmed/22022239 http://dx.doi.org/10.1371/journal.pcbi.1002169 Text en Fitzpatrick et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fitzpatrick, Anthony W. Knowles, Tuomas P. J. Waudby, Christopher A. Vendruscolo, Michele Dobson, Christopher M. Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation |
title | Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation |
title_full | Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation |
title_fullStr | Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation |
title_full_unstemmed | Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation |
title_short | Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation |
title_sort | inversion of the balance between hydrophobic and hydrogen bonding interactions in protein folding and aggregation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192805/ https://www.ncbi.nlm.nih.gov/pubmed/22022239 http://dx.doi.org/10.1371/journal.pcbi.1002169 |
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