Evidence for a hydrogen sulfide-sensing E3 ligase in yeast

Area of Science:

• * Molecular biology
• * Biochemistry

Background:

• * Sulfur amino acid biosynthesis in yeast is regulated by the transcription factor Met4.
• * The SCFMet30 E3 ubiquitin ligase represses Met4 activity during sulfur abundance through ubiquitination.
• * The precise mechanism by which Met30 senses cellular sulfur status remains unclear.

Purpose of the Study:

• * To elucidate the mechanism by which the F-box protein Met30 senses sulfur availability.
• * To understand how SCFMet30 activity is tuned to regulate the MET gene transcriptional program.
• * To identify the molecular components involved in sulfur sensing by Met30.

Main Methods:

• * Investigated the role of the trans-sulfuration pathway in Met30 regulation.
• * Assessed the response of Met30 to hydrogen sulfide in vivo.
• * Identified key cysteine residues in Met30's WD-40 repeat region crucial for sulfur sensing.

Main Results:

• * Met30 activity is regulated by flux through the trans-sulfuration pathway.
• * Hydrogen sulfide directly induces ubiquitination of Met4 by SCFMet30.
• * Specific cysteine residues within Met30's WD-40 repeats are critical for sensing cellular sulfur levels.

Conclusions:

• * SCFMet30 dynamically senses sulfur metabolite flow via the trans-sulfuration pathway.
• * This sensing mechanism allows for precise regulation of cysteine and methionine biosynthesis.
• * The findings reveal a novel pathway for sulfur homeostasis in yeast.