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Title: Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [3];  [1];  [1];  [4]
  1. Univ. of California, San Diego, La Jolla, CA (United States). Dept. of Bioengineering
  2. Univ. of California, San Diego, La Jolla, CA (United States). Div. of Biological Sciences
  3. Univ. of California, San Diego, La Jolla, CA (United States). Dept. of Bioengineering and Bioinformatics and Systems Biology
  4. 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
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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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1498117
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, Issue 43; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 45 works
Citation information provided by
Web of Science

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Cited By (12)

Use of genome-scale models to get new insights into the marine actinomycete genus Salinispora journal January 2019
Adaptive evolution reveals a tradeoff between growth rate and oxidative stress during naphthoquinone-based aerobic respiration journal November 2019
COBRAme: A computational framework for genome-scale models of metabolism and gene expression journal July 2018
Machine learning applied to enzyme turnover numbers reveals protein structural correlates and improves metabolic models journal December 2018
DynamicME: dynamic simulation and refinement of integrated models of metabolism and protein expression journal January 2019
A physical model of cell metabolism journal May 2018
Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli journal December 2019
OxyR Is a Convergent Target for Mutations Acquired during Adaptation to Oxidative Stress-Prone Metabolic States journal October 2019
Advances in metabolic modeling of oleaginous microalgae journal September 2018
Proteostasis collapse is a driver of cell aging and death journal October 2019
Cellular responses to reactive oxygen species are predicted from molecular mechanisms journal July 2019
Growth‐driven displacement of protein aggregates along the cell length ensures partitioning to both daughter cells in Caulobacter crescentus journal April 2019

Figures / Tables (4)

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59 BASIC BIOLOGICAL SCIENCES
thermoadaptation
proteome allocation
bacterial growth law
genome-scale model
molecular chaperones