PT  - JOURNAL ARTICLE
AU  - Roger L. Chang
AU  - Julian A. Stanley
AU  - Matthew C. Robinson
AU  - Joel W. Sher
AU  - Zhanwen Li
AU  - Yujia A. Chan
AU  - Ashton R. Omdahl
AU  - Ruddy Wattiez
AU  - Adam Godzik
AU  - Sabine Matallana-Surget
TI  - Unraveling Oxidative Stress Resistance: Molecular Properties Govern Proteome Vulnerability
AID  - 10.1101/2020.03.09.983213
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.09.983213
4099  - http://biorxiv.org/content/early/2020/03/09/2020.03.09.983213.short
4100  - http://biorxiv.org/content/early/2020/03/09/2020.03.09.983213.full
AB  - 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.One Sentence Summary Proteins differ in intrinsic susceptibility to oxidation, a mode of evolutionary adaptation for stress tolerance in bacteria.