cytoplasm protein quality control / heterochromatin boundary formation / cytoplasm protein quality control by the ubiquitin-proteasome system / protein K29-linked ubiquitination / nuclear protein quality control by the ubiquitin-proteasome system / HECT-type E3 ubiquitin transferase / protein K11-linked ubiquitination / DNA repair-dependent chromatin remodeling / ubiquitin-ubiquitin ligase activity / progesterone receptor signaling pathway ...cytoplasm protein quality control / heterochromatin boundary formation / cytoplasm protein quality control by the ubiquitin-proteasome system / protein K29-linked ubiquitination / nuclear protein quality control by the ubiquitin-proteasome system / HECT-type E3 ubiquitin transferase / protein K11-linked ubiquitination / DNA repair-dependent chromatin remodeling / ubiquitin-ubiquitin ligase activity / progesterone receptor signaling pathway / protein K48-linked ubiquitination / negative regulation of smoothened signaling pathway / ubiquitin binding / positive regulation of protein import into nucleus / protein polyubiquitination / positive regulation of canonical Wnt signaling pathway / ubiquitin protein ligase activity / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA repair / DNA damage response / positive regulation of gene expression / chromatin / perinuclear region of cytoplasm / protein-containing complex / RNA binding / zinc ion binding / nucleoplasm / membrane / nucleus / cytoplasm / cytosol 類似検索 - 分子機能
: / E3 ubiquitin ligase EDD, ubiquitin-associated domain / E3 ubiquitin ligase EDD / Polyadenylate-binding protein/Hyperplastic disc protein / Poly-adenylate binding protein, unique domain / Poly(A)-binding protein C-terminal (PABC) domain profile. / C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein. / PABC (PABP) domain / Zinc finger, UBR-type / Zinc finger UBR-type profile. ...: / E3 ubiquitin ligase EDD, ubiquitin-associated domain / E3 ubiquitin ligase EDD / Polyadenylate-binding protein/Hyperplastic disc protein / Poly-adenylate binding protein, unique domain / Poly(A)-binding protein C-terminal (PABC) domain profile. / C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein. / PABC (PABP) domain / Zinc finger, UBR-type / Zinc finger UBR-type profile. / Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway / Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II / HECT domain / HECT, E3 ligase catalytic domain / HECT-domain (ubiquitin-transferase) / HECT domain profile. / Domain Homologous to E6-AP Carboxyl Terminus with 類似検索 - ドメイン・相同性
H2020 Marie Curie Actions of the European Commission
847548
European Union
引用
ジャーナル: EMBO J / 年: 2023 タイトル: Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5. 著者: Zuzana Hodáková / Irina Grishkovskaya / Hanna L Brunner / Derek L Bolhuis / Katarina Belačić / Alexander Schleiffer / Harald Kotisch / Nicholas G Brown / David Haselbach / 要旨: UBR5 is a nuclear E3 ligase that ubiquitinates a vast range of substrates for proteasomal degradation. This HECT domain-containing ubiquitin ligase has recently been identified as an important ...UBR5 is a nuclear E3 ligase that ubiquitinates a vast range of substrates for proteasomal degradation. This HECT domain-containing ubiquitin ligase has recently been identified as an important regulator of oncogenes, e.g., MYC, but little is known about its structure or mechanisms of substrate engagement and ubiquitination. Here, we present the cryo-EM structure of human UBR5, revealing an α-solenoid scaffold with numerous protein-protein interacting motifs, assembled into an antiparallel dimer that adopts further oligomeric states. Using cryo-EM processing tools, we observe the dynamic nature of the UBR5 catalytic domain, which we postulate is important for its enzymatic activity. We characterise the proteasomal nuclear import factor AKIRIN2 as an interacting protein and propose UBR5 as an efficient ubiquitin chain elongator. This preference for ubiquitinated substrates and several distinct domains for protein-protein interactions may explain how UBR5 is linked to several different signalling pathways and cancers. Together, our data expand on the limited knowledge of the structure and function of HECT E3 ligases.