Cysteine perthiosulfenic acid (Cys-SSOH): A novel intermediate in thiol-based redox signaling?

Heppner, D. E. and Hristova, M. and Ida, T. and Mijuskovic, A. and Dustin, C. M. and Bogdándi, Virág and Nagy, Péter (2017) Cysteine perthiosulfenic acid (Cys-SSOH): A novel intermediate in thiol-based redox signaling? REDOX BIOLOGY, 14. pp. 379-385. ISSN 2213-2317

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Abstract

The reversible oxidation of protein cysteine residues (Cys-SH) is a key reaction in cellular redox signaling involving initial formation of sulfenic acids (Cys-SOH), which are commonly detected using selective dimedone-based probes. Here, we report that significant portions of dimedone-tagged proteins are susceptible to cleavage by DTT reflecting the presence of perthiosulfenic acid species (Cys-SSOH) due to similar oxidation of hydropersulfides (Cys-SSH), since Cys-S-dimedone adducts are stable toward DTT. Combined studies using molecular modeling, mass spectrometry, and cell-based experiments indicate that Cys-SSH are readily oxidized to Cys-SSOH, which forms stable adducts with dimedone-based probes. We additionally confirm the presence of Cys-SSH within protein tyrosine kinases such as EGFR, and their apparent oxidation to Cys-SSOH in response NADPH oxidase activation, suggesting that such Cys-SSH oxidation may represent a novel, as yet uncharacterized, event in redox-based signaling.

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