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 confirmed the critical role of the persulfide group in the thermostability and Zn-binding affinity of GIF/MT-3. The present discovery raises the fascinating possibility that the function of other Zn-binding proteins is controlled by sulfane sulfur.

More information

Identifiers

ORCID for George Devitt: orcid.org/0000-0001-7179-4459

ORCID for Sumeet Mahajan: orcid.org/0000-0001-8923-6666

Catalogue record

Export record

Altmetrics