8JE1

An asymmetry dimer of the Cul2-Rbx1-EloBC-FEM1B ubiquitin ligase complexed with BEX2

Summary for 8JE1

• Entry DOI: 10.2210/pdb8je1/pdb
• EMDB information: 36182
• Descriptor: Cullin-2, Elongin-B, Elongin-C, ... (6 entities in total)
• Functional Keywords: complex, e3 ubiquitin ligase, cullin, oligomer, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 375176.04

Authors

Dai, Z.,Liang, L.,Yin, Y.X. (deposition date: 2023-05-15, release date: 2024-02-28, Last modification date: 2024-04-03)

Primary citation

Dai, Z.,Liang, L.,Wang, W.,Zuo, P.,Yu, S.,Liu, Y.,Zhao, X.,Lu, Y.,Jin, Y.,Zhang, F.,Ding, D.,Deng, W.,Yin, Y.
Structural insights into the ubiquitylation strategy of the oligomeric CRL2 FEM1B E3 ubiquitin ligase.
Embo J., 43:1089-1109, 2024

PubMed Abstract: Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2 in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2 is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2 according to substrates with different scales.

PubMed: 38360992
DOI: 10.1038/s44318-024-00047-y

Experimental method

ELECTRON MICROSCOPY (3.95 Å)