Design principles of a membrane-spanning ubiquitin ligase - PubMed
3 hours ago
- #Hedgehog signaling
- #cryo-EM structure
- #E3 ubiquitin ligase
- Receptor-type E3 ubiquitin ligases, such as the MEGF8-MOSMO-MGRN1 (MMM) complex, regulate intracellular ubiquitylation in response to extracellular signals.
- The MMM complex inhibits Hedgehog signaling by ubiquitylating Smoothened (SMO), a GPCR, reducing its presence at primary cilia.
- Structural analysis reveals the MMM complex uses a long helix to engage SMO via an intramembrane degron and positions an activated RING domain beneath the plasma membrane for targeted ubiquitylation.
- Mutations in MEGF8 are linked to multi-organ birth defects, highlighting the importance of this E3 ligase in development.