Key result
H2S rapidly persulfidates the zinc finger protein TTP in an O2-dependent manner, inhibiting its ability to bind TNFα mRNA in vitro and modulating TNFα in vivo.
Hypothesis-generating for H2S effects on TTP; in vivo studies needed before any clinical consideration.
H2S is a gaseous signaling molecule that modifies cysteine residues in proteins to form persulfides (P‐SSH). One family of proteins modified by H2S are zinc finger (ZF) proteins, which contain multiple zinc‐coordinating cysteine residues. Herein, we report the reactivity of H2S with a ZF protein called tristetraprolin (TTP). Rapid persulfidation leading to complete thiol oxidation of TTP mediated by H2S was observed by low‐temperature ESI‐MS and fluorescence spectroscopy. Persulfidation of TTP required O2 , which reacts with H2S to form superoxide, as detected by ESI‐MS, a hydroethidine fluorescence assay, and EPR spin trapping. H2S was observed to inhibit TTP function (binding to TNFα mRNA) by an in vitro fluorescence anisotropy assay and to modulate TNFα in vivo. H2S was unreactive towards TTP when the protein was bound to RNA, thus suggesting a protective effect of RNA.
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Lange et al. (2019) studied this question. H2S was evaluated on Reactivity of H2S with TTP and its effect on TTP function. H2S rapidly persulfidates the zinc finger protein TTP in an O2-dependent manner, inhibiting its ability to bind TNFα mRNA in vitro and modulating TNFα in vivo.
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