Zinc Fingers are a General Target for Persulfidation by Hydrogen Sulfide (H2S)
AuthorStoltzfus, Andrew T.
Worth, Madison M.
Filipovic, Milos R.
Michel, Sarah L.J.
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AbstractPersulfidation (or "sulfhydration") of protein thiols by the gasotransmitter hydrogen sulfide (H2S) has been recently established as an important signaling event associated with oxidative stress and cellular aging. While H2S, mostly bisulfide (HS-) anion at physiological pH, likely does not persulfidate protein thiols directly due to incompatible electric potential, it may act through small- molecule thiols (ex: glutathione) to add a sulfur to cysteine thiols (CysSH → CysSSH). This highly reactive persulfide species can alter protein function and/or scavenge intracellular radical species during oxidative stress by direct reaction with radicals. Zinc finger proteins (ZFs) are potential targets for this PTM as they contain Cys-rich zinc-binding domains and our laboratory has previously reported the direct reaction of the ZF protein TTP with H2S. This reaction requires O2 and involves in-situ persulfidation. To understand how general ZF persulfidation is, we applied a persulfide- specific proteomics approach and observed a trend between Cys content of ZF domains and frequency of persulfidation. A series of TTP variants were prepared and analyzed for H2S reactivity via cryo-electrospray ionization mass spectrometry, as well as UV-visible, circular dichroism, and fluorescence spectroscopies. We found that all peptide variants bound Zn(II) and were persulfidated by H2S to some extent, with higher Cys content contributing to greater persulfide labeling and ROS in the -CCCH and -CCCC peptides. Current work is focused on proteomic classification of persulfidated ZFs and elucidating the radical mechanism of this PTM using chemical tags, fluorescence, and spin-traps.
DescriptionUMB Grad Gathering, October 13, 2023
Rights/TermsAttribution-NonCommercial-NoDerivatives 4.0 International
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/20945
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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International