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Mol Cell Proteomics. 2014 Mar;13(3):849-59. doi: 10.1074/mcp.M113.032953. Epub 2014 Jan 15.

Alkylation damage by lipid electrophiles targets functional protein systems.

Author information

1
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232;

Abstract

Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions.

PMID:
24429493
PMCID:
PMC3945913
DOI:
10.1074/mcp.M113.032953
[Indexed for MEDLINE]
Free PMC Article

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