This study elucidates structures and mechanisms of complexes formed by the two non-canonical cullin-RING ubiquitin E3 ligases (CRLs), CUL7 and CUL9. CUL7 forms a unique CRL E3-E3 assembly that inverts classic roles, with CUL7 acting as substrate receptor and the F-box protein as adaptor, linking to the catalytical CUL1-RBX1 complex, mediating TP53 ubiquitylation. CUL9 forms a 1.8 MDa hexameric assembly that unifies two E3 ligase classes (cullin-RING and RBR) in one complex. Our studies opened a new chapter on how CRLs use E3-E3 super-assemblies for substrate ubiquitylation.     «

This study elucidates structures and mechanisms of complexes formed by the two non-canonical cullin-RING ubiquitin E3 ligases (CRLs), CUL7 and CUL9. CUL7 forms a unique CRL E3-E3 assembly that inverts classic roles, with CUL7 acting as substrate receptor and the F-box protein as adaptor, linking to the catalytical CUL1-RBX1 complex, mediating TP53 ubiquitylation. CUL9 forms a 1.8 MDa hexameric assembly that unifies two E3 ligase classes (cullin-RING and RBR) in one complex. Our studies opened a...     »