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

Roger L. Chang, Julian A. Stanley, Matthew C. Robinson, Joel W. Sher, Zhanwen Li, Yujia A. Chan, Ashton R. Omdahl, Ruddy Wattiez, Adam Godzik, Sabine Matallana-Surget

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish (US)
Article numbere104523
JournalEMBO Journal
Volume39
Issue number23
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

Keywords

  • Deinococcus radiodurans
  • oxidative stress
  • protein carbonyl
  • radioresistance
  • structural systems biology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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