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An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins
We previously showed the existence of selective pressure against protein aggregation by the enrichment of aggregation-opposing ‘gatekeeper’ residues at strategic places along the sequence of proteins. Here we analyzed the relationship between protein lifetime and protein aggregation by combining exp...
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/PMC3121684/ https://www.ncbi.nlm.nih.gov/pubmed/21731483 http://dx.doi.org/10.1371/journal.pcbi.1002090 |
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author | De Baets, Greet Reumers, Joke Delgado Blanco, Javier Dopazo, Joaquin Schymkowitz, Joost Rousseau, Frederic |
author_facet | De Baets, Greet Reumers, Joke Delgado Blanco, Javier Dopazo, Joaquin Schymkowitz, Joost Rousseau, Frederic |
author_sort | De Baets, Greet |
collection | PubMed |
description | We previously showed the existence of selective pressure against protein aggregation by the enrichment of aggregation-opposing ‘gatekeeper’ residues at strategic places along the sequence of proteins. Here we analyzed the relationship between protein lifetime and protein aggregation by combining experimentally determined turnover rates, expression data, structural data and chaperone interaction data on a set of more than 500 proteins. We find that selective pressure on protein sequences against aggregation is not homogeneous but that short-living proteins on average have a higher aggregation propensity and fewer chaperone interactions than long-living proteins. We also find that short-living proteins are more often associated to deposition diseases. These findings suggest that the efficient degradation of high-turnover proteins is sufficient to preclude aggregation, but also that factors that inhibit proteasomal activity, such as physiological ageing, will primarily affect the aggregation of short-living proteins. |
format | Online Article Text |
id | pubmed-3121684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31216842011-06-30 An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins De Baets, Greet Reumers, Joke Delgado Blanco, Javier Dopazo, Joaquin Schymkowitz, Joost Rousseau, Frederic PLoS Comput Biol Research Article We previously showed the existence of selective pressure against protein aggregation by the enrichment of aggregation-opposing ‘gatekeeper’ residues at strategic places along the sequence of proteins. Here we analyzed the relationship between protein lifetime and protein aggregation by combining experimentally determined turnover rates, expression data, structural data and chaperone interaction data on a set of more than 500 proteins. We find that selective pressure on protein sequences against aggregation is not homogeneous but that short-living proteins on average have a higher aggregation propensity and fewer chaperone interactions than long-living proteins. We also find that short-living proteins are more often associated to deposition diseases. These findings suggest that the efficient degradation of high-turnover proteins is sufficient to preclude aggregation, but also that factors that inhibit proteasomal activity, such as physiological ageing, will primarily affect the aggregation of short-living proteins. Public Library of Science 2011-06-23 /pmc/articles/PMC3121684/ /pubmed/21731483 http://dx.doi.org/10.1371/journal.pcbi.1002090 Text en De Baets 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 De Baets, Greet Reumers, Joke Delgado Blanco, Javier Dopazo, Joaquin Schymkowitz, Joost Rousseau, Frederic An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins |
title | An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins |
title_full | An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins |
title_fullStr | An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins |
title_full_unstemmed | An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins |
title_short | An Evolutionary Trade-Off between Protein Turnover Rate and Protein Aggregation Favors a Higher Aggregation Propensity in Fast Degrading Proteins |
title_sort | evolutionary trade-off between protein turnover rate and protein aggregation favors a higher aggregation propensity in fast degrading proteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121684/ https://www.ncbi.nlm.nih.gov/pubmed/21731483 http://dx.doi.org/10.1371/journal.pcbi.1002090 |
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