Article

Protein structure, amino acid composition and sequence determine proteome vulnerability to oxidation-induced damage

Details

Citation

Chang RL, Stanley JA, Robinson MC, Sher JW, Li Z, Chan YA, Omdahl AR, Wattiez R, Godzik A & Matallana-Surget S (2020) Protein structure, amino acid composition and sequence determine proteome vulnerability to oxidation-induced damage. EMBO Journal, 39 (23), Art. No.: e104523. https://doi.org/10.15252/embj.2020104523

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

Journal
EMBO Journal: Volume 39, Issue 23

StatusPublished
Publication date01/12/2020
Publication date online19/10/2020
Date accepted by journal22/09/2020
URLhttp://hdl.handle.net/1893/31863
ISSN0261-4189
eISSN1460-2075

People (1)

Dr Sabine Matallana-Surget

Dr Sabine Matallana-Surget

Associate Professor, Biological and Environmental Sciences