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Direct Zinc Finger Protein Persulfidation by H 2 S Is Facilitated by Zn 2+
Author(s) -
Lange Mike,
Ok Kiwon,
Shimberg Geoffrey D.,
Bursac Biljana,
Markó Lajos,
IvanovićBurmazović Ivana,
Michel Sarah L. J.,
Filipovic Milos R.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201900823
Subject(s) - chemistry , zinc finger , tristetraprolin , cysteine , zinc , electron paramagnetic resonance , rna , fluorescence , in vitro , reactivity (psychology) , thiol , messenger rna , molecule , in vivo , stereochemistry , biochemistry , rna binding protein , enzyme , organic chemistry , nuclear magnetic resonance , transcription factor , biology , gene , medicine , physics , alternative medicine , quantum mechanics , pathology , microbiology and biotechnology
H 2 S is a gaseous signaling molecule that modifies cysteine residues in proteins to form persulfides (P‐SSH). One family of proteins modified by H 2 S are zinc finger (ZF) proteins, which contain multiple zinc‐coordinating cysteine residues. Herein, we report the reactivity of H 2 S with a ZF protein called tristetraprolin (TTP). Rapid persulfidation leading to complete thiol oxidation of TTP mediated by H 2 S was observed by low‐temperature ESI‐MS and fluorescence spectroscopy. Persulfidation of TTP required O 2 , which reacts with H 2 S to form superoxide, as detected by ESI‐MS, a hydroethidine fluorescence assay, and EPR spin trapping. H 2 S was observed to inhibit TTP function (binding to TNFα mRNA) by an in vitro fluorescence anisotropy assay and to modulate TNFα in vivo. H 2 S was unreactive towards TTP when the protein was bound to RNA, thus suggesting a protective effect of RNA.
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