9KBD

Cryo-EM structure of the CUL1-RBX1-SKP1-FBXO3 SCF ubiquition ligase complex

Summary for 9KBD

• Entry DOI: 10.2210/pdb9kbd/pdb
• EMDB information: 62222
• Descriptor: S-phase kinase-associated protein 1, F-box only protein 3, E3 ubiquitin-protein ligase RBX1, ... (4 entities in total)
• Functional Keywords: ubiquitination e3 ligase, cryo-em, protein binding, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 171075.89

Authors

Wei, J.,Xu, C. (deposition date: 2024-10-30, release date: 2025-02-19, Last modification date: 2025-07-23)

Primary citation

Wei, J.,Xu, C.
Structural Insight Into the SKP1-CUL1-FBXO3-RBX1 Complex.
Proteins, 93:1290-1294, 2025

PubMed Abstract: The cryo-EM structure of human SCF, which consists of CUL1, RBX1, SKP1 and FBXO3 was solved at a nominal resolution of 3.70 Å. Although a previous study reported the crystal structure of the FBXO3 ApaG domain, how FBXO3 is incorporated into the SCF complex remains elusive. In the cryo-EM structure of SCF, the F-box domain of FBXO3 primarily associates with SKP1 via extensive hydrophobic interactions and interacts with the N-terminal region of CUL1 via hydrophobic interactions. The weak cryo-EM map of the RBX1 globular region is close to the FBXO3 ApaG domain, suggesting that unmodified SCF exhibits a closed conformation and that CUL1 neddylation is likely required to achieve high E3 activity. The structural study provides insight into the assembly of SCF and its activation mediated by CUL1 neddylation.

PubMed: 39921442
DOI: 10.1002/prot.26809

Experimental method

ELECTRON MICROSCOPY (3.7 Å)