8WQE

Cryo-EM structure of CUL2-RBX1-ELOB-ELOC-FEM1B bound with the C-degron of CUX1 (conformation 1)

Summary for 8WQE

• Entry DOI: 10.2210/pdb8wqe/pdb
• EMDB information: 37742
• Descriptor: Cullin-2, Protein fem-1 homolog B, Elongin-C, ... (7 entities in total)
• Functional Keywords: e3 ubiquitin ligase, pro/c-degron, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 391994.70

Authors

Chen, X.,Zhang, K.,Xu, C. (deposition date: 2023-10-11, release date: 2024-04-03, Last modification date: 2024-05-08)

Primary citation

Chen, X.,Raiff, A.,Li, S.,Guo, Q.,Zhang, J.,Zhou, H.,Timms, R.T.,Yao, X.,Elledge, S.J.,Koren, I.,Zhang, K.,Xu, C.
Mechanism of Psi-Pro/C-degron recognition by the CRL2 FEM1B ubiquitin ligase.
Nat Commun, 15:3558-3558, 2024

PubMed Abstract: The E3 ligase-degron interaction determines the specificity of the ubiquitin‒proteasome system. We recently discovered that FEM1B, a substrate receptor of Cullin 2-RING ligase (CRL2), recognizes C-degrons containing a C-terminal proline. By solving several cryo-EM structures of CRL2 bound to different C-degrons, we elucidate the dimeric assembly of the complex. Furthermore, we reveal distinct dimerization states of unmodified and neddylated CRL2 to uncover the NEDD8-mediated activation mechanism of CRL2. Our research also indicates that, FEM1B utilizes a bipartite mechanism to recognize both the C-terminal proline and an upstream aromatic residue within the substrate. These structural findings, complemented by in vitro ubiquitination and in vivo cell-based assays, demonstrate that CRL2-mediated polyubiquitination and subsequent protein turnover depend on both FEM1B-degron interactions and the dimerization state of the E3 ligase complex. Overall, this study deepens our molecular understanding of how Cullin-RING E3 ligase substrate selection mediates protein turnover.

PubMed: 38670995
DOI: 10.1038/s41467-024-47890-5

Experimental method

ELECTRON MICROSCOPY (3.38 Å)