Structure of the CUL1-RBX1-SKP1-FBXO4 SCF ubiquitin ligase complex

Cullin-RING E3 ubiquitin ligases (CRLs) constitute the largest family of ubiquitin ligase and play important roles in regulation of proteostasis. Here we presented the cryo-EM structure of CRL1^FBXO4, a member of Cullin-1 E3 ligase. CRL1^FBXO4 adopts a homodimer architecture. Structural analysis revealed that in the CRL1^FBXO4 protomer, the substrate recognition subunit FBXO4 interacts both the adaptor protein SKP1, and the scaffold protein CUL1 via hydrophobic and electrostatic interactions. Two FBXO4 forms a domain-swapped dimer in the CRL1^FBXO4 structure, which constitutes the basis for the dimerization of CRL1^FBXO4. Inspired by the cryo-EM density, we modeled the architecture of whole CRL1^FBXO4 as a symmetrical dimer, which provides insights into CRL1^FBXO4-medaited turnover of oncogene proteins.