MUB1-RAD6-UBR2 ubiquitin ligase complex / RAD6-UBR2 ubiquitin ligase complex / sno(s)RNA transcription / Rad6-Rad18 complex / regulation of dipeptide transport / UBR1-RAD6 ubiquitin ligase complex / HULC complex / error-free postreplication DNA repair / proteasome regulatory particle binding / stress-induced homeostatically regulated protein degradation pathway ...MUB1-RAD6-UBR2 ubiquitin ligase complex / RAD6-UBR2 ubiquitin ligase complex / sno(s)RNA transcription / Rad6-Rad18 complex / regulation of dipeptide transport / UBR1-RAD6 ubiquitin ligase complex / HULC complex / error-free postreplication DNA repair / proteasome regulatory particle binding / stress-induced homeostatically regulated protein degradation pathway / ubiquitin-dependent protein catabolic process via the N-end rule pathway / meiotic DNA double-strand break formation / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / cytoplasm protein quality control by the ubiquitin-proteasome system / mitochondria-associated ubiquitin-dependent protein catabolic process / E3 ubiquitin ligases ubiquitinate target proteins / telomere maintenance via recombination / proteasome regulatory particle, base subcomplex / ribosome-associated ubiquitin-dependent protein catabolic process / DNA duplex unwinding / E2 ubiquitin-conjugating enzyme / error-free translesion synthesis / sporulation resulting in formation of a cellular spore / proteasome binding / mitotic G1 DNA damage checkpoint signaling / protein monoubiquitination / ubiquitin conjugating enzyme activity / Antigen processing: Ubiquitination & Proteasome degradation / subtelomeric heterochromatin formation / cellular response to unfolded protein / error-prone translesion synthesis / ERAD pathway / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / NOTCH3 Activation and Transmission of Signal to the Nucleus / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Regulation of pyruvate metabolism / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / Regulation of PTEN localization / NRIF signals cell death from the nucleus / Regulation of BACH1 activity / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / EGFR downregulation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / TNFR1-induced NF-kappa-B signaling pathway / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D Similarity search - Function
E3 ubiquitin-protein ligase UBR-like, C-terminal / Proteolysis_6 C-terminal / E3 ubiquitin-protein ligase UBR1-like / Putative zinc finger in N-recognin (UBR box) / Zinc finger, UBR-type / Zinc finger UBR-type profile. / Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway / : / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. ...E3 ubiquitin-protein ligase UBR-like, C-terminal / Proteolysis_6 C-terminal / E3 ubiquitin-protein ligase UBR1-like / Putative zinc finger in N-recognin (UBR box) / Zinc finger, UBR-type / Zinc finger UBR-type profile. / Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway / : / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. / Ubiquitin-conjugating enzyme E2, catalytic domain homologues / Ubiquitin-conjugating enzyme E2 / Ubiquitin-conjugating enzyme / Ubiquitin-conjugating (UBC) core domain profile. / Ubiquitin-conjugating enzyme/RWD-like / : / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily Similarity search - Domain/homology
Journal: Nature / Year: 2021 Title: Structural insights into Ubr1-mediated N-degron polyubiquitination. Authors: Man Pan / Qingyun Zheng / Tian Wang / Lujun Liang / Junxiong Mao / Chong Zuo / Ruichao Ding / Huasong Ai / Yuan Xie / Dong Si / Yuanyuan Yu / Lei Liu / Minglei Zhao / Abstract: The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation. In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N- ...The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation. In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N-degron pathway. How Ubr1 mediates the initiation of ubiquitination and the elongation of the ubiquitin chain in a linkage-specific manner through a single E2 ubiquitin-conjugating enzyme (Ubc2) remains unknown. Here we developed chemical strategies to mimic the reaction intermediates of the first and second ubiquitin transfer steps, and determined the cryo-electron microscopy structures of Ubr1 in complex with Ubc2, ubiquitin and two N-degron peptides, representing the initiation and elongation steps of ubiquitination. Key structural elements, including a Ubc2-binding region and an acceptor ubiquitin-binding loop on Ubr1, were identified and characterized. These structures provide mechanistic insights into the initiation and elongation of ubiquitination catalysed by Ubr1.
History
Deposition
Sep 20, 2021
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Header (metadata) release
Nov 24, 2021
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Map release
Nov 24, 2021
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Update
Dec 22, 2021
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Current status
Dec 22, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
EMPIAR-10905 (Title: Single-particle cryoEM data of yeast Ubr1 (apo) / Data size: 3.2 TB Data #1: Unaligned movie data of yeast Ubr1 (apo) [micrographs - multiframe])
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