Chemoselective Proteomics, Zinc Fingers, and a Zinc(II) Model for H<sub>2</sub>S Mediated Persulfidation
Andrew T. Stoltzfus, Jasper G. Ballot, Thibaut Vignane, Hongye Li, Madison M. Worth, Ludovic Muller, Maxime A. Siegler, Maureen A. Kane, Miloš R. Filipović, David P. Goldberg, Sarah L. J. Michel
Abstract
Abstract The gasotransmitter hydrogen sulfide (H 2 S) is thought to be involved in the post‐translational modification of cysteine residues to produce reactive persulfides. A persulfide‐specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by Zn II , O 2 , and H 2 S, with intermediates involving oxygen‐ and sulfur‐based radicals detected by mass spectrometry and optical spectroscopies. A small molecule Zn II complex exhibits analogous reactivity with H 2 S and O 2 , giving a persulfidated product. These data show that Zn II is not just a biological structural element, but also plays a critical role in mediating H 2 S‐dependent persulfidation. ZF persulfidation appears to be a general post‐translational modification and a possible conduit for H 2 S signaling. This work has implications for our understanding of H 2 S‐mediated signaling and the regulation of ZFs in cellular physiology and development.