7YW1

crystal structure of UBE2O

Summary for 7YW1

• Entry DOI: 10.2210/pdb7yw1/pdb
• Descriptor: (E3-independent) E2 ubiquitin-conjugating enzyme UBE2O (1 entity in total)
• Functional Keywords: ube2o, cytosolic protein
• Biological source: Trametes pubescens
• Total number of polymer chains: 2
• Total formula weight: 205885.91

Authors

Fu, Z.,Zhu, W.,Huang, H. (deposition date: 2022-08-20, release date: 2023-08-30, Last modification date: 2025-02-26)

Primary citation

Huang, H.,Zhu, W.,Huang, B.,Fu, Z.,Xiong, Y.,Cao, D.,Ye, Y.,Chang, Q.,Li, W.,Li, L.,Zhou, H.,Niu, X.,Zhang, W.
Structural insights into the biochemical mechanism of the E2/E3 hybrid enzyme UBE2O.
Structure, 33:274-288.e4, 2025

PubMed Abstract: The E2/E3 hybrid enzyme UBE2O plays important roles in key biological events, but its autoubiquitination mechanism remains largely unclear. In this study, we determined the crystal structures of full-length (FL) UBE2O from Trametes pubescens (tp) and its ubiquitin-conjugating (UBC) domain. The dimeric FL-tpUBE2O structure revealed interdomain interactions between the conserved regions (CR1-CR2) and UBC. The dimeric intermolecular and canonical ubiquitin/UBC interactions are mechanistically important for UBE2O functions in catalyzing the formation of free polyubiquitin chains and substrate ubiquitination. Beyond dimerization, autoubiquitination within the CR1-CR2 domain also regulates tpUBE2O activity. Additionally, we show that tpUBE2O catalyzes the formation of all seven types of polyubiquitin chains in vitro. The CR1-CR2/UBC and canonical ubiquitin/UBC interactions are important for the polyubiquitination of AMP-activated protein kinase α2 (AMPKα2) by human UBE2O (hUBE2O), which leads to tumorigenesis. These structural insights lay the groundwork for understanding UBE2O's mechanisms and developing structure-based therapeutics targeting UBE2O.

PubMed: 39740670
DOI: 10.1016/j.str.2024.12.002

Experimental method

X-RAY DIFFRACTION (3.27 Å)