Daniel Liebler
Faculty Member
Last active: 2/15/2016

Alkylation damage by lipid electrophiles targets functional protein systems.

Codreanu SG, Ullery JC, Zhu J, Tallman KA, Beavers WN, Porter NA, Marnett LJ, Zhang B, Liebler DC
Mol Cell Proteomics. 2014 13 (3): 849-59

PMID: 24429493 · PMCID: PMC3945913 · DOI:10.1074/mcp.M113.032953

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.

MeSH Terms (10)

Aldehydes Alkylation Cell Line Electrons Glutathione Humans Lipids Protein Interaction Maps Proteins Proteome

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