LRRC58 defines an E3 ubiquitin ligase complex sensitive to cysteine abundance - PubMed
4 hours ago
- #ubiquitin ligase
- #cysteine homeostasis
- #neurodevelopment
- LRRC58 is identified as a substrate adaptor for a Cullin-RING E3 ubiquitin ligase complex that responds to cysteine levels.
- In high cysteine conditions, LRRC58 is ubiquitinated and degraded by the proteasome, inhibiting its activity.
- During cysteine deprivation, LRRC58 stabilizes to target CDO1, a key enzyme in cysteine catabolism, for degradation.
- CDO1 degradation protects cells from ferroptosis when cysteine is scarce.
- Mutations in CDO1 linked to human neurodevelopmental disorders produce proteins that resist LRRC58-mediated degradation, highlighting the axis's role in neural development.
- Structural insights into the CDO1-LRRC58 interaction were validated through saturation mutagenesis, pinpointing critical residues in LRRC58's C-terminus.