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Defining the hydrogen peroxide-dependent redoxome in human cells

ABSTRACT: 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/.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Epithelial Cell, Cell Culture

SUBMITTER: Jing Yang

LAB HEAD: Jing Yang

PROVIDER: PXD006657 | Pride | 2021-02-18

REPOSITORIES: Pride

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			Action	DRS
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C1.pepXML	Pepxml
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C1.raw	Raw
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C2.pepXML	Pepxml
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C2.raw	Raw
	A0288_klc_20140708m_A431_Redoxome_H2O2_BR1_C3.pepXML	Pepxml

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Systematic and quantitative assessment of hydrogen peroxide reactivity with cysteines across human proteomes

Project description: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/.

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