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Proteome Folding Kinetics Is Limited by Protein Halflife

How heterogeneous are proteome folding timescales and what physical principles, if any, dictate its limits? We answer this by predicting copy number weighted folding speed distribution – using the native topology – for E.coli and Yeast proteome. E.coli and Yeast proteomes yield very similar distribu...

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Detalles Bibliográficos
Autores principales: Zou, Taisong, Williams, Nickolas, Ozkan, S. Banu, Ghosh, Kingshuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231061/
https://www.ncbi.nlm.nih.gov/pubmed/25393560
http://dx.doi.org/10.1371/journal.pone.0112701
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author Zou, Taisong
Williams, Nickolas
Ozkan, S. Banu
Ghosh, Kingshuk
author_facet Zou, Taisong
Williams, Nickolas
Ozkan, S. Banu
Ghosh, Kingshuk
author_sort Zou, Taisong
collection PubMed
description How heterogeneous are proteome folding timescales and what physical principles, if any, dictate its limits? We answer this by predicting copy number weighted folding speed distribution – using the native topology – for E.coli and Yeast proteome. E.coli and Yeast proteomes yield very similar distributions with average folding times of 100 milliseconds and 170 milliseconds, respectively. The topology-based folding time distribution is well described by a diffusion-drift mutation model on a flat-fitness landscape in free energy barrier between two boundaries: i) the lowest barrier height determined by the upper limit of folding speed and ii) the highest barrier height governed by the lower speed limit of folding. While the fastest time scale of the distribution is near the experimentally measured speed limit of 1 microsecond (typical of barrier-less folders), we find the slowest folding time to be around seconds ([Image: see text]8 seconds for Yeast distribution), approximately an order of magnitude less than the fastest halflife (approximately 2 minutes) in the Yeast proteome. This separation of timescale implies even the fastest degrading protein will have moderately high (96%) probability of folding before degradation. The overall agreement with the flat-fitness landscape model further hints that proteome folding times did not undergo additional major selection pressures – to make proteins fold faster – other than the primary requirement to “sufficiently beat the clock” against its lifetime. Direct comparison between the predicted folding time and experimentally measured halflife further shows 99% of the proteome have a folding time less than their corresponding lifetime. These two findings together suggest that proteome folding kinetics may be bounded by protein halflife.
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spelling pubmed-42310612014-11-18 Proteome Folding Kinetics Is Limited by Protein Halflife Zou, Taisong Williams, Nickolas Ozkan, S. Banu Ghosh, Kingshuk PLoS One Research Article How heterogeneous are proteome folding timescales and what physical principles, if any, dictate its limits? We answer this by predicting copy number weighted folding speed distribution – using the native topology – for E.coli and Yeast proteome. E.coli and Yeast proteomes yield very similar distributions with average folding times of 100 milliseconds and 170 milliseconds, respectively. The topology-based folding time distribution is well described by a diffusion-drift mutation model on a flat-fitness landscape in free energy barrier between two boundaries: i) the lowest barrier height determined by the upper limit of folding speed and ii) the highest barrier height governed by the lower speed limit of folding. While the fastest time scale of the distribution is near the experimentally measured speed limit of 1 microsecond (typical of barrier-less folders), we find the slowest folding time to be around seconds ([Image: see text]8 seconds for Yeast distribution), approximately an order of magnitude less than the fastest halflife (approximately 2 minutes) in the Yeast proteome. This separation of timescale implies even the fastest degrading protein will have moderately high (96%) probability of folding before degradation. The overall agreement with the flat-fitness landscape model further hints that proteome folding times did not undergo additional major selection pressures – to make proteins fold faster – other than the primary requirement to “sufficiently beat the clock” against its lifetime. Direct comparison between the predicted folding time and experimentally measured halflife further shows 99% of the proteome have a folding time less than their corresponding lifetime. These two findings together suggest that proteome folding kinetics may be bounded by protein halflife. Public Library of Science 2014-11-13 /pmc/articles/PMC4231061/ /pubmed/25393560 http://dx.doi.org/10.1371/journal.pone.0112701 Text en © 2014 Zou 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
Zou, Taisong
Williams, Nickolas
Ozkan, S. Banu
Ghosh, Kingshuk
Proteome Folding Kinetics Is Limited by Protein Halflife
title Proteome Folding Kinetics Is Limited by Protein Halflife
title_full Proteome Folding Kinetics Is Limited by Protein Halflife
title_fullStr Proteome Folding Kinetics Is Limited by Protein Halflife
title_full_unstemmed Proteome Folding Kinetics Is Limited by Protein Halflife
title_short Proteome Folding Kinetics Is Limited by Protein Halflife
title_sort proteome folding kinetics is limited by protein halflife
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231061/
https://www.ncbi.nlm.nih.gov/pubmed/25393560
http://dx.doi.org/10.1371/journal.pone.0112701
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