Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein.

ABSTRACT: Cysteine-bound sulfane sulfur atoms in proteins have received much attention as key factors in cellular redox homeostasis. However, the role of sulfane sulfur in zinc regulation has been underinvestigated. In this study, we identified growth inhibitory factor (GIF)/metallothionein-3 (MT-3) as a sulfane sulfur-binding protein from mouse brain. We also report here that cysteine-bound sulfane sulfur atoms serve as ligands to hold and release zinc ions in GIF/MT-3 with an unexpected C-S-S-Zn structure. Oxidation of such a zinc/persulfide cluster in Zn₇GIF/MT-3 results in the release of zinc ions, and intramolecular tetrasulfide bridges in apo-GIF/MT-3 efficiently undergo S-S bond cleavage by thioredoxin to regenerate Zn₇GIF/MT-3. Three-dimensional molecular modeling confi

SUBMITTER: Shinkai Y 

PROVIDER: S-EPMC12618007 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature