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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 |
Sumario: | 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. |
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