Cryo-EM structures of UBA6 reveal mechanisms of E1-E2 specificity and dual FAT10/ubiquitin thioester transfer - PubMed
4 hours ago
- #Proteostasis
- #Cryo-EM
- #Ubiquitin
- Cryo-EM structures of UBA6 reveal mechanisms of E1-E2 specificity and dual FAT10/ubiquitin thioester transfer.
- UBA1 and UBA6 define parallel ubiquitin (Ub) activation systems with non-overlapping roles in Ub and ubiquitin-like protein (Ubl) signaling.
- UBA6 activates the Ubl FAT10, linking Ub signaling to immune-regulated proteostasis.
- UBA6 achieves E2 specificity through coordinated contributions of the UFD and SCCH domains, contrasting with UBA1's UFD-dominated selectivity.
- An inositol hexakisphosphate (InsP6)-binding site unique to UBA6 stabilizes an expanded SCCH cleft, pre-organizing the enzyme for selective E2 engagement.
- The findings define principles for E1-E2 recognition and identify InsP6 as a cofactor in the Ub-like conjugation network.