@article{7c06474099ea4083a5c376662b1919df,
title = "Protein structure, amino acid composition and sequence determine proteome vulnerability to oxidation-induced damage",
abstract = "Oxidative stress alters cell viability, from microorganism irradiation sensitivity to human aging and neurodegeneration. Deleterious effects of protein carbonylation by reactive oxygen species (ROS) make understanding molecular properties determining ROS susceptibility essential. The radiation-resistant bacterium Deinococcus radiodurans accumulates less carbonylation than sensitive organisms, making it a key model for deciphering properties governing oxidative stress resistance. We integrated shotgun redox proteomics, structural systems biology, and machine learning to resolve properties determining protein damage by γ-irradiation in Escherichia coli and D. radiodurans at multiple scales. Local accessibility, charge, and lysine enrichment accurately predict ROS susceptibility. Lysine, methionine, and cysteine usage also contribute to ROS resistance of the D. radiodurans proteome. Our model predicts proteome maintenance machinery, and proteins protecting against ROS are more resistant in D. radiodurans. Our findings substantiate that protein-intrinsic protection impacts oxidative stress resistance, identifying causal molecular properties.",
keywords = "Deinococcus radiodurans, oxidative stress, protein carbonyl, radioresistance, structural systems biology",
author = "Chang, {Roger L.} and Stanley, {Julian A.} and Robinson, {Matthew C.} and Sher, {Joel W.} and Zhanwen Li and Chan, {Yujia A.} and Omdahl, {Ashton R.} and Ruddy Wattiez and Adam Godzik and Sabine Matallana-Surget",
note = "Funding Information: Roger Chang especially thanks Dr. Pamela Silver (Harvard) who as his Postdoctoral Advisor allowed and supported this unique, independently conceived effort. As such, Dr. Silver provided laboratory resources, feedback on the work, comments on the manuscript and full support of this independent publication. We also thank Dr. Debora Marks (Harvard) for advice on machine learning, data analysis and feedback on the manuscript; Dr. James Collins (MIT) for facilitating γ‐irradiator access; Dr. James Weaver (Wyss Institute) for fabricating the irradiator rack; and Dr. Fatma Elzahraa Eid (Broad Institute) for proofreading the manuscript. Computational modeling was enabled by the HMS O2 high performance compute cluster. Funding: This work was funded by the Gordon and Betty Moore Foundation GBMF 2550.04 Life Sciences Research Foundation post‐doctoral fellowship and the Wyss Institute. The UMons proteomic facility was supported by the Belgian National Funds for Scientific Research (FNRS). Funding Information: Roger Chang especially thanks Dr. Pamela Silver (Harvard) who as his Postdoctoral Advisor allowed and supported this unique, independently conceived effort. As such, Dr. Silver provided laboratory resources, feedback on the work, comments on the manuscript and full support of this independent publication. We also thank Dr. Debora Marks (Harvard) for advice on machine learning, data analysis and feedback on the manuscript; Dr. James Collins (MIT) for facilitating γ-irradiator access; Dr. James Weaver (Wyss Institute) for fabricating the irradiator rack; and Dr. Fatma Elzahraa Eid (Broad Institute) for proofreading the manuscript. Computational modeling was enabled by the HMS O2 high performance compute cluster. Funding: This work was funded by the Gordon and Betty Moore Foundation GBMF 2550.04 Life Sciences Research Foundation post-doctoral fellowship and the Wyss Institute. The UMons proteomic facility was supported by the Belgian National Funds for Scientific Research (FNRS). Publisher Copyright: {\textcopyright} 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license",
year = "2020",
month = dec,
day = "1",
doi = "10.15252/embj.2020104523",
language = "English (US)",
volume = "39",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "23",
}