Evolutionary Optimization of Protein Folding
Nature has shaped the make up of proteins since their appearance, 3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated f...
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| Format: | Online |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547816/ |
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pubmed-3547816 |
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pubmed-35478162013-01-22 Evolutionary Optimization of Protein Folding Debès, Cédric Wang, Minglei Caetano-Anollés, Gustavo Gräter, Frauke Research Article Nature has shaped the make up of proteins since their appearance, 3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last 1.5 billion years that began during the “big bang” of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions. Public Library of Science 2013-01-17 /pmc/articles/PMC3547816/ /pubmed/23341762 http://dx.doi.org/10.1371/journal.pcbi.1002861 Text en © 2013 Debès 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Debès, Cédric Wang, Minglei Caetano-Anollés, Gustavo Gräter, Frauke |
| spellingShingle |
Debès, Cédric Wang, Minglei Caetano-Anollés, Gustavo Gräter, Frauke Evolutionary Optimization of Protein Folding |
| author_facet |
Debès, Cédric Wang, Minglei Caetano-Anollés, Gustavo Gräter, Frauke |
| author_sort |
Debès, Cédric |
| title |
Evolutionary Optimization of Protein Folding |
| title_short |
Evolutionary Optimization of Protein Folding |
| title_full |
Evolutionary Optimization of Protein Folding |
| title_fullStr |
Evolutionary Optimization of Protein Folding |
| title_full_unstemmed |
Evolutionary Optimization of Protein Folding |
| title_sort |
evolutionary optimization of protein folding |
| description |
Nature has shaped the make up of proteins since their appearance, 3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last 1.5 billion years that began during the “big bang” of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547816/ |
| _version_ |
1611947823298772992 |