Systematic and Quantitative Assessment of Hydrogen Peroxide Reactivity With Cysteines Across Human Proteomes.
Ling FuKeke LiuMingan SunCaiping TianRui SunCarlos Morales BetanzosKeri A TallmanNed A PorterYong YangDianjing GuoDaniel C LieblerJing YangPublished in: Molecular & cellular proteomics : MCP (2017)
Protein cysteinyl residues are the mediators of hydrogen peroxide (H2O2)-dependent redox signaling. However, site-specific mapping of the selectivity and dynamics of these redox reactions in cells poses a major analytical challenge. Here we describe a chemoproteomic platform to systematically and quantitatively analyze the reactivity of thousands of cysteines toward H2O2 in human cells. We identified >900 H2O2-sensitive cysteines, which are defined as the H2O2-dependent redoxome. Although redox sites associated with antioxidative and metabolic functions are consistent, most of the H2O2-dependent redoxome varies dramatically between different cells. Structural analyses reveal that H2O2-sensitive cysteines are less conserved than their redox-insensitive counterparts and display distinct sequence motifs, structural features, and potential for crosstalk with lysine modifications. Notably, our chemoproteomic platform also provides an opportunity to predict oxidation-triggered protein conformational changes. The data are freely accessible as a resource at http://redox.ncpsb.org/OXID/.
Keyphrases
- hydrogen peroxide
- nitric oxide
- induced apoptosis
- cell cycle arrest
- electron transfer
- amino acid
- high throughput
- endothelial cells
- high resolution
- endoplasmic reticulum stress
- oxidative stress
- small molecule
- single cell
- mass spectrometry
- molecular dynamics
- transcription factor
- gene expression
- cell proliferation
- liquid chromatography
- machine learning
- climate change
- electronic health record