Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation
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 individual protein affects the overall functional state of the proteome. Overall, these results expand our view of cellular regulation, from targeted specific control mechanisms tomore »
- Authors:
-
- Univ. of California, San Diego, La Jolla, CA (United States). Dept. of Bioengineering
- Univ. of California, San Diego, La Jolla, CA (United States). Div. of Biological Sciences
- Univ. of California, San Diego, La Jolla, CA (United States). Dept. of Bioengineering and Bioinformatics and Systems Biology
- Univ. of California, San Diego, La Jolla, CA (United States). Dept. of Bioengineering and Dept. of Pediatrics; Technical Univ. of Denmark, Lyngby (Denmark). Novo Nordisk Foundation Center for Biosustainability
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1498117
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 114; Journal Issue: 43; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; thermoadaptation; proteome allocation; bacterial growth law; genome-scale model; molecular chaperones
Citation Formats
Chen, Ke, Gao, Ye, Mih, Nathan, O’Brien, Edward J., Yang, Laurence, and Palsson, Bernhard O. Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation. United States: N. p., 2017.
Web. doi:10.1073/pnas.1705524114.
Chen, Ke, Gao, Ye, Mih, Nathan, O’Brien, Edward J., Yang, Laurence, & Palsson, Bernhard O. Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation. United States. https://doi.org/10.1073/pnas.1705524114
Chen, Ke, Gao, Ye, Mih, Nathan, O’Brien, Edward J., Yang, Laurence, and Palsson, Bernhard O. Tue .
"Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation". United States. https://doi.org/10.1073/pnas.1705524114. https://www.osti.gov/servlets/purl/1498117.
@article{osti_1498117,
title = {Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation},
author = {Chen, Ke and Gao, Ye and Mih, Nathan and O’Brien, Edward J. and Yang, Laurence and Palsson, Bernhard O.},
abstractNote = {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 individual protein affects the overall functional state of the proteome. Overall, these results expand our view of cellular regulation, from targeted specific control mechanisms to global regulation through a web of nonspecific competing interactions that modulate the optimal reallocation of cellular resources. As a result, the methodology developed in this study enables genome-scale integration of environment-dependent protein properties and a proteome-wide study of cellular stress responses.},
doi = {10.1073/pnas.1705524114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 43,
volume = 114,
place = {United States},
year = {Tue Oct 10 00:00:00 EDT 2017},
month = {Tue Oct 10 00:00:00 EDT 2017}
}
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Figures / Tables:
Figure 1: FoldME reconstruction and validation. (A) Elementary model reactions for the three folding pathways. The flux going through each reaction is denoted Vreaction_label, and the coupling constraints are explained in the text. (B) Illustration of how temperature dependence of each biophysical property is combined to compute their collective effectmore »
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