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Updated: Jan 27, 2026

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Direct Zinc Finger Protein Persulfidation by H2 S Is Facilitated by Zn2
Mike Lange1,2, Kiwon Ok3, Geoffrey D Shimberg3
1Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, 91058, Erlangen, Germany.
Abstract:
H2 S is a gaseous signaling molecule that modifies cysteine residues in proteins to form persulfides (P-SSH). One family of proteins modified by H2 S are zinc finger (ZF) proteins, which contain multiple zinc-coordinating cysteine residues. Herein, we report the reactivity of H2 S with a ZF protein called tristetraprolin (TTP). Rapid persulfidation leading to complete thiol oxidation of TTP mediated by H2 S was observed by low-temperature ESI-MS and fluorescence spectroscopy. Persulfidation of TTP required O2 , which reacts with H2 S to form superoxide, as detected by ESI-MS, a hydroethidine fluorescence assay, and EPR spin trapping. H2 S was observed to inhibit TTP function (binding to TNFα mRNA) by an in vitro fluorescence anisotropy assay and to modulate TNFα in vivo. H2 S was unreactive towards TTP when the protein was bound to RNA, thus suggesting a protective effect of RNA.
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