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Quantitative influence of macromolecular crowding on gene regulation kinetics

We introduce macromolecular crowding quantitatively into the model for kinetics of gene regulation in Escherichia coli. We analyse and compute the specific-site searching time for 180 known transcription factors (TFs) regulating 1300 operons. The time is between 160 s (e.g. for SoxS M(w) = 12.91 kDa...

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Autores principales: Tabaka, Marcin, Kalwarczyk, Tomasz, Hołyst, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902910/
https://www.ncbi.nlm.nih.gov/pubmed/24121687
http://dx.doi.org/10.1093/nar/gkt907
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author Tabaka, Marcin
Kalwarczyk, Tomasz
Hołyst, Robert
author_facet Tabaka, Marcin
Kalwarczyk, Tomasz
Hołyst, Robert
author_sort Tabaka, Marcin
collection PubMed
description We introduce macromolecular crowding quantitatively into the model for kinetics of gene regulation in Escherichia coli. We analyse and compute the specific-site searching time for 180 known transcription factors (TFs) regulating 1300 operons. The time is between 160 s (e.g. for SoxS M(w) = 12.91 kDa) and 1550 s (e.g. for PepA(6) of M(w) = 329.28 kDa). Diffusion coefficients for one-dimensional sliding are between [Image: see text] for large proteins up to [Image: see text] for small monomers or dimers. Three-dimensional diffusion coefficients in the cytoplasm are 2 orders of magnitude larger than 1D sliding coefficients, nevertheless the sliding enhances the binding rates of TF to specific sites by 1–2 orders of magnitude. The latter effect is due to ubiquitous non-specific binding. We compare the model to experimental data for LacI repressor and find that non-specific binding of the protein to DNA is activation- and not diffusion-limited. We show that the target location rate by LacI repressor is optimized with respect to microscopic rate constant for association to non-specific sites on DNA. We analyse the effect of oligomerization of TFs and DNA looping effects on searching kinetics. We show that optimal searching strategy depends on TF abundance.
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spelling pubmed-39029102014-01-27 Quantitative influence of macromolecular crowding on gene regulation kinetics Tabaka, Marcin Kalwarczyk, Tomasz Hołyst, Robert Nucleic Acids Res Computational Biology We introduce macromolecular crowding quantitatively into the model for kinetics of gene regulation in Escherichia coli. We analyse and compute the specific-site searching time for 180 known transcription factors (TFs) regulating 1300 operons. The time is between 160 s (e.g. for SoxS M(w) = 12.91 kDa) and 1550 s (e.g. for PepA(6) of M(w) = 329.28 kDa). Diffusion coefficients for one-dimensional sliding are between [Image: see text] for large proteins up to [Image: see text] for small monomers or dimers. Three-dimensional diffusion coefficients in the cytoplasm are 2 orders of magnitude larger than 1D sliding coefficients, nevertheless the sliding enhances the binding rates of TF to specific sites by 1–2 orders of magnitude. The latter effect is due to ubiquitous non-specific binding. We compare the model to experimental data for LacI repressor and find that non-specific binding of the protein to DNA is activation- and not diffusion-limited. We show that the target location rate by LacI repressor is optimized with respect to microscopic rate constant for association to non-specific sites on DNA. We analyse the effect of oligomerization of TFs and DNA looping effects on searching kinetics. We show that optimal searching strategy depends on TF abundance. Oxford University Press 2014-01 2013-10-08 /pmc/articles/PMC3902910/ /pubmed/24121687 http://dx.doi.org/10.1093/nar/gkt907 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Computational Biology
Tabaka, Marcin
Kalwarczyk, Tomasz
Hołyst, Robert
Quantitative influence of macromolecular crowding on gene regulation kinetics
title Quantitative influence of macromolecular crowding on gene regulation kinetics
title_full Quantitative influence of macromolecular crowding on gene regulation kinetics
title_fullStr Quantitative influence of macromolecular crowding on gene regulation kinetics
title_full_unstemmed Quantitative influence of macromolecular crowding on gene regulation kinetics
title_short Quantitative influence of macromolecular crowding on gene regulation kinetics
title_sort quantitative influence of macromolecular crowding on gene regulation kinetics
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902910/
https://www.ncbi.nlm.nih.gov/pubmed/24121687
http://dx.doi.org/10.1093/nar/gkt907
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