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Chemoproteomics Reveals Chemical Diversity and Dynamics of 4-Oxo-2-nonenal Modifications in Cells

ABSTRACT: 4-Oxo-2-nonenal (ONE) derived from lipid peroxidation modifies nucleophiles and transduces redox signaling by its reactions with proteins. However, the molecular interactions between ONE and complex proteomes and their dynamics in situ remain largely unknown. Here we de-scribe a quantitative chemoproteomic analysis of protein adduction by ONE in cells, in which the cellular target profile of ONE is mimicked by its alkynyl surrogate. The analysis reveals four types of ONE-derived modifications in cells, including ketoamide and Schiff-base adducts to lysine, Michael adducts to cysteine, and a novel pyrrole adducts to cysteine. ONE-derived adducts co-localize and crosstalk with many histone marks and redox sensitive sites. All four types of modifications derived from ONE can be reversed site-specifically in cells. In summary, our study provides much-needed mechanistic insights into the cellular signaling and potential toxicities associated with this important lipid derived electrophile.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Jing Yang

LAB HEAD: Jing Yang

PROVIDER: PXD006680 | Pride | 2022-02-24

REPOSITORIES: Pride

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			Action	DRS
	JY_RKO_aONE_PC0h_20150419_BR1_T1.mzIdentML	Mzid
	JY_RKO_aONE_PC0h_20150419_BR1_T1.raw	Raw
	JY_RKO_aONE_PC0h_20150419_BR1_T2.mzIdentML	Mzid
	JY_RKO_aONE_PC0h_20150419_BR1_T2.raw	Raw
	JY_RKO_aONE_PC0h_20150419_BR2_T1.mzIdentML	Mzid

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4-Oxo-2-nonenal Adductions in Cells

Project description:4-Oxo-2-nonenal (ONE) derived from lipid peroxidation modifies nucleophiles and transduces redox signaling by its reactions with proteins. However, the molecular interactions between ONE and complex proteomes and their dynamics in situ remain largely unknown. Here we de-scribe a quantitative chemoproteomic analysis of protein adduction by ONE in cells, in which the cellular target profile of ONE is mimicked by its alkynyl surrogate. The analysis reveals four types of ONE-derived modifications in cells, including ketoamide and Schiff-base adducts to lysine, Michael adducts to cysteine, and a novel pyrrole adducts to cysteine. ONE-derived adducts co-localize and crosstalk with many histone marks and redox sensitive sites. All four types of modifications derived from ONE can be reversed site-specifically in cells. In summary, our study provides much-needed mechanistic insights into the cellular signaling and potential toxicities associated with this important lipid derived electrophile.

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