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8gxr

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crystal structure of UBC domain of UBE2O

Structural highlights

8gxr is a 4 chain structure with sequence from Trametes pubescens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A1M2VY70_TRAPU

Publication Abstract from PubMed

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 alpha2 (AMPKalpha2) 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.

Structural insights into the biochemical mechanism of the E2/E3 hybrid enzyme UBE2O.,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 Structure. 2025 Feb 6;33(2):274-288.e4. doi: 10.1016/j.str.2024.12.002. Epub 2024 , Dec 30. PMID:39740670^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. 2025 Feb 6;33(2):274-288.e4. PMID:39740670 doi:10.1016/j.str.2024.12.002