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Non-ergodicity of a globular protein extending beyond its functional timescale
Internal motions of folded proteins have been assumed to be ergodic, i.e., that the dynamics of a single protein molecule averaged over a very long time resembles that of an ensemble. Here, by performing single-molecule fluorescence resonance energy transfer (smFRET) experiments and molecular dynami...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400594/ https://www.ncbi.nlm.nih.gov/pubmed/36091909 http://dx.doi.org/10.1039/d2sc03069a |
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author | Li, Jun Xie, JingFei Godec, Aljaž Weninger, Keith R. Liu, Cong Smith, Jeremy C. Hong, Liang |
author_facet | Li, Jun Xie, JingFei Godec, Aljaž Weninger, Keith R. Liu, Cong Smith, Jeremy C. Hong, Liang |
author_sort | Li, Jun |
collection | PubMed |
description | Internal motions of folded proteins have been assumed to be ergodic, i.e., that the dynamics of a single protein molecule averaged over a very long time resembles that of an ensemble. Here, by performing single-molecule fluorescence resonance energy transfer (smFRET) experiments and molecular dynamics (MD) simulations of a multi-domain globular protein, cytoplasmic protein-tyrosine phosphatase (SHP2), we demonstrate that the functional inter-domain motion is observationally non-ergodic over the time spans 10(−12) to 10(−7) s and 10(−1) to 10(2) s. The difference between observational non-ergodicity and simple non-convergence is discussed. In comparison, a single-strand DNA of similar size behaves ergodically with an energy landscape resembling a one-dimensional linear chain. The observed non-ergodicity results from the hierarchical connectivity of the high-dimensional energy landscape of the protein molecule. As the characteristic time for the protein to conduct its dephosphorylation function is ∼10 s, our findings suggest that, due to the non-ergodicity, individual, seemingly identical protein molecules can be dynamically and functionally different. |
format | Online Article Text |
id | pubmed-9400594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-94005942022-09-08 Non-ergodicity of a globular protein extending beyond its functional timescale Li, Jun Xie, JingFei Godec, Aljaž Weninger, Keith R. Liu, Cong Smith, Jeremy C. Hong, Liang Chem Sci Chemistry Internal motions of folded proteins have been assumed to be ergodic, i.e., that the dynamics of a single protein molecule averaged over a very long time resembles that of an ensemble. Here, by performing single-molecule fluorescence resonance energy transfer (smFRET) experiments and molecular dynamics (MD) simulations of a multi-domain globular protein, cytoplasmic protein-tyrosine phosphatase (SHP2), we demonstrate that the functional inter-domain motion is observationally non-ergodic over the time spans 10(−12) to 10(−7) s and 10(−1) to 10(2) s. The difference between observational non-ergodicity and simple non-convergence is discussed. In comparison, a single-strand DNA of similar size behaves ergodically with an energy landscape resembling a one-dimensional linear chain. The observed non-ergodicity results from the hierarchical connectivity of the high-dimensional energy landscape of the protein molecule. As the characteristic time for the protein to conduct its dephosphorylation function is ∼10 s, our findings suggest that, due to the non-ergodicity, individual, seemingly identical protein molecules can be dynamically and functionally different. The Royal Society of Chemistry 2022-08-04 /pmc/articles/PMC9400594/ /pubmed/36091909 http://dx.doi.org/10.1039/d2sc03069a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Li, Jun Xie, JingFei Godec, Aljaž Weninger, Keith R. Liu, Cong Smith, Jeremy C. Hong, Liang Non-ergodicity of a globular protein extending beyond its functional timescale |
title | Non-ergodicity of a globular protein extending beyond its functional timescale |
title_full | Non-ergodicity of a globular protein extending beyond its functional timescale |
title_fullStr | Non-ergodicity of a globular protein extending beyond its functional timescale |
title_full_unstemmed | Non-ergodicity of a globular protein extending beyond its functional timescale |
title_short | Non-ergodicity of a globular protein extending beyond its functional timescale |
title_sort | non-ergodicity of a globular protein extending beyond its functional timescale |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400594/ https://www.ncbi.nlm.nih.gov/pubmed/36091909 http://dx.doi.org/10.1039/d2sc03069a |
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