Cryo‐EM structure of the chain‐elongating E3 ubiquitin ligase UBR5

• DOI: 10.15252/embj.2022113348
• Publication Date: 2023-07-06T10:01:22Z
• Authors: Zuzana Hodáková; Irina Grishkovskaya; Hanna L Brunner; Derek L Bolhuis; Katarina Belačić; Alexander Schleiffer; Harald Kotisch; Nicholas G Brown; David Haselbach
• Keywords: Ubiquitin-Protein Ligases; Chain (unit)

UBR5 is a nuclear E3 ligase that ubiquitinates vast range of substrates for proteasomal degradation. This HECT domain-containing ubiquitin has recently been identified as an important regulator oncogenes, e.g., MYC, but little known about its structure or mechanisms substrate engagement and ubiquitination. Here, we present the cryo-EM human UBR5, revealing α-solenoid scaffold with numerous protein-protein interacting motifs, assembled into antiparallel dimer adopts further oligomeric states. Using processing tools, observe dynamic nature catalytic domain, which postulate enzymatic activity. We characterise import factor AKIRIN2 protein propose efficient chain elongator. preference ubiquitinated several distinct domains interactions may explain how linked to different signalling pathways cancers. Together, our data expand on limited knowledge function ligases.