Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation

Proceedings of the National Academy of Sciences of the United States of America
Ke ChenBernhard O Palsson

Abstract

Maintenance of a properly folded proteome is critical for bacterial survival at notably different growth temperatures. Understanding the molecular basis of thermoadaptation has progressed in two main directions, the sequence and structural basis of protein thermostability and the mechanistic principles of protein quality control assisted by chaperones. Yet we do not fully understand how structural integrity of the entire proteome is maintained under stress and how it affects cellular fitness. To address this challenge, we reconstruct a genome-scale protein-folding network for Escherichia coli and formulate a computational model, FoldME, that provides statistical descriptions of multiscale cellular response consistent with many datasets. FoldME simulations show (i) that the chaperones act as a system when they respond to unfolding stress rather than achieving efficient folding of any single component of the proteome, (ii) how the proteome is globally balanced between chaperones for folding and the complex machinery synthesizing the proteins in response to perturbation, (iii) how this balancing determines growth rate dependence on temperature and is achieved through nonspecific regulation, and (iv) how thermal instability of the ...Continue Reading

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Citations

Feb 15, 2018·Bioinformatics·Nathan MihBernhard O Palsson
Jul 6, 2018·PLoS Computational Biology·Colton J LloydBernhard O Palsson
Sep 27, 2018·FEMS Microbiology Letters·Ilyas KabimoldayevDonghyuk Kim
Oct 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Mantu SantraAdam M R de Graff
Nov 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Amitesh AnandBernhard O Palsson
Oct 28, 2019·Molecular Biology and Evolution·Amitesh AnandBernhard O Palsson
Jun 25, 2020·Proteomics·Sanjeev DahalLaurence Yang
Sep 12, 2018·Biotechnology for Biofuels·Juan D Tibocha-BonillaKarsten Zengler
May 31, 2018·Scientific Reports·Jorge Fernandez-de-Cossio-Diaz, Alexei Vazquez
Jan 23, 2019·BMC Systems Biology·Carolina A ContadorJuan A Asenjo
Sep 23, 2020·Nature Reviews. Microbiology·Xin FangBernhard O Palsson
Jul 5, 2019·Proceedings of the National Academy of Sciences of the United States of America·Laurence YangBernhard O Palsson
Jan 10, 2021·Nature Communications·Gang LiJens Nielsen
Dec 30, 2020·Microorganisms·Daniel Craig ZielinskiBernhard O Palsson
Mar 10, 2021·NPJ Systems Biology and Applications·Francis MairetHidde de Jong
May 2, 2021·Biophysical Journal·Rostam M RazbanEugene I Shakhnovich
Aug 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Anjan RoyRami Pugatch
Aug 16, 2021·Journal of Molecular Biology·Evan T Powers, Lila M Gierasch

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