8gxr: Difference between revisions
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/A0A1M2VY70_TRAPU A0A1M2VY70_TRAPU] | [https://www.uniprot.org/uniprot/A0A1M2VY70_TRAPU A0A1M2VY70_TRAPU] | ||
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== 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<ref>PMID:39740670</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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<div class="pdbe-citations 8gxr" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 22:27, 26 February 2025
crystal structure of UBC domain of UBE2Ocrystal structure of UBC domain of UBE2O
Structural highlights
FunctionPublication Abstract from PubMedThe 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
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