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Yorodumi- EMDB-17713: Catalytic module of human CTLH E3 ligase bound to multiphosphoryl... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-17713 | ||||||||||||
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Title | Catalytic module of human CTLH E3 ligase bound to multiphosphorylated UBE2H~ubiquitin | ||||||||||||
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Sample |
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Keywords | E3 ubiquitin ligase / E2 ubiquitin-conjugating enzyme / phosphorylation / CTLH / GID / UBE2H / LIGASE | ||||||||||||
Function / homology | Function and homology information GID complex / enucleate erythrocyte development / actomyosin contractile ring / (E3-independent) E2 ubiquitin-conjugating enzyme / negative regulation of myeloid cell apoptotic process / protein K11-linked ubiquitination / cell cycle / E2 ubiquitin-conjugating enzyme / erythrocyte maturation / regulation of mitotic cell cycle ...GID complex / enucleate erythrocyte development / actomyosin contractile ring / (E3-independent) E2 ubiquitin-conjugating enzyme / negative regulation of myeloid cell apoptotic process / protein K11-linked ubiquitination / cell cycle / E2 ubiquitin-conjugating enzyme / erythrocyte maturation / regulation of mitotic cell cycle / ubiquitin conjugating enzyme activity / protein K48-linked ubiquitination / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / cytoskeleton organization / 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 / Regulation of NF-kappa B signaling / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / activated TAK1 mediates p38 MAPK activation / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Negative regulators of DDX58/IFIH1 signaling / Deactivation of the beta-catenin transactivating complex / Degradation of DVL / CDK-mediated phosphorylation and removal of Cdc6 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Regulation of signaling by CBL / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Fanconi Anemia Pathway / Hh mutants are degraded by ERAD / Negative regulation of FGFR3 signaling / SCF(Skp2)-mediated degradation of p27/p21 / Degradation of AXIN Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||||||||
Authors | Chrustowicz J / Sherpa D / Prabu RJ / Schulman BA | ||||||||||||
Funding support | Germany, European Union, 3 items
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Citation | Journal: Mol Cell / Year: 2024 Title: Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies. Authors: Jakub Chrustowicz / Dawafuti Sherpa / Jerry Li / Christine R Langlois / Eleftheria C Papadopoulou / D Tung Vu / Laura A Hehl / Özge Karayel / Viola Beier / Susanne von Gronau / Judith ...Authors: Jakub Chrustowicz / Dawafuti Sherpa / Jerry Li / Christine R Langlois / Eleftheria C Papadopoulou / D Tung Vu / Laura A Hehl / Özge Karayel / Viola Beier / Susanne von Gronau / Judith Müller / J Rajan Prabu / Matthias Mann / Gary Kleiger / Arno F Alpi / Brenda A Schulman / Abstract: Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ...Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ubiquitin ligases and their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development. Here, cryoelectron microscopy (cryo-EM), biochemistry, and cell biology reveal this exquisitely specific E3-E2 pairing through an unconventional catalytic assembly and auxiliary interactions 70-100 Å away, mediated by E2 multisite phosphorylation. Rather than dynamic polyelectrostatic interactions reported for other ubiquitylation complexes, multiple Ubc8/UBE2H phosphorylation sites within acidic CK2-targeted sequences specifically anchor the E2 C termini to E3 basic patches. Positions of phospho-dependent interactions relative to the catalytic domains correlate across evolution. Overall, our data show that phosphorylation-dependent multivalency establishes a specific E3-E2 partnership, is antagonistic with dephosphorylation, rigidifies the catalytic centers within a flexing GID E3-substrate assembly, and facilitates substrate collision with ubiquitylation active sites. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_17713.map.gz | 6.3 MB | EMDB map data format | |
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Header (meta data) | emd-17713-v30.xml emd-17713.xml | 23.1 KB 23.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_17713_fsc.xml | 9.7 KB | Display | FSC data file |
Images | emd_17713.png | 106.6 KB | ||
Masks | emd_17713_msk_1.map | 76.8 MB | Mask map | |
Filedesc metadata | emd-17713.cif.gz | 6.7 KB | ||
Others | emd_17713_additional_1.map.gz emd_17713_half_map_1.map.gz emd_17713_half_map_2.map.gz | 66.3 MB 59.9 MB 59.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-17713 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17713 | HTTPS FTP |
-Validation report
Summary document | emd_17713_validation.pdf.gz | 718.3 KB | Display | EMDB validaton report |
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Full document | emd_17713_full_validation.pdf.gz | 717.9 KB | Display | |
Data in XML | emd_17713_validation.xml.gz | 16.8 KB | Display | |
Data in CIF | emd_17713_validation.cif.gz | 22 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17713 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17713 | HTTPS FTP |
-Related structure data
Related structure data | 8pjnMC 8pmqC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_17713.map.gz / Format: CCP4 / Size: 76.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.851 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_17713_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: #1
File | emd_17713_additional_1.map | ||||||||||||
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-Half map: #2
File | emd_17713_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_17713_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of human CTLHSR4 E3 ligase bound to engineered ARMC8-spec...
Entire | Name: Complex of human CTLHSR4 E3 ligase bound to engineered ARMC8-specific VH and multiphosphorylated UBE2H~ubiquitin |
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Components |
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-Supramolecule #1: Complex of human CTLHSR4 E3 ligase bound to engineered ARMC8-spec...
Supramolecule | Name: Complex of human CTLHSR4 E3 ligase bound to engineered ARMC8-specific VH and multiphosphorylated UBE2H~ubiquitin type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 Details: Map obtained by focus refinement over the catalytic module (RMND5A, MAEA) and UBE2H~ubiquitin |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 600 KDa |
-Macromolecule #1: E3 ubiquitin-protein transferase RMND5A
Macromolecule | Name: E3 ubiquitin-protein transferase RMND5A / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 44.043449 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MDQCVTVERE LEKVLHKFSG YGQLCERGLE ELIDYTGGLK HEILQSHGQD AELSGTLSLV LTQCCKRIKD TVQKLASDHK DIHSSVSRV GKAIDKNFDS DISSVGIDGC WQADSQRLLN EVMVEHFFRQ GMLDVAEELC QESGLSVDPS QKEPFVELNR I LEALKVRV ...String: MDQCVTVERE LEKVLHKFSG YGQLCERGLE ELIDYTGGLK HEILQSHGQD AELSGTLSLV LTQCCKRIKD TVQKLASDHK DIHSSVSRV GKAIDKNFDS DISSVGIDGC WQADSQRLLN EVMVEHFFRQ GMLDVAEELC QESGLSVDPS QKEPFVELNR I LEALKVRV LRPALEWAVS NREMLIAQNS SLEFKLHRLY FISLLMGGTT NQREALQYAK NFQPFALNHQ KDIQVLMGSL VY LRQGIEN SPYVHLLDAN QWADICDIFT RDACALLGLS VESPLSVSFS AGCVALPALI NIKAVIEQRQ CTGVWNQKDE LPI EVDLGK KCWYHSIFAC PILRQQTTDN NPPMKLVCGH IISRDALNKM FNGSKLKCPY CPMEQSPGDA KQIFF UniProtKB: E3 ubiquitin-protein transferase RMND5A |
-Macromolecule #2: Ubiquitin-conjugating enzyme E2 H
Macromolecule | Name: Ubiquitin-conjugating enzyme E2 H / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: E2 ubiquitin-conjugating enzyme |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 21.260986 KDa |
Recombinant expression | Organism: Trichoplusia (butterflies/moths) |
Sequence | String: MSSPSPGKRR MDTDVVKLIE SKHEVTILGG LNEFVVKFYG PQGTPYEGGV WKVRVDLPDK YPFKSPSIGF MNKIFHPNID EASGTVKLD VINQTWTALY DLTNIFESFL PQLLAYPNPI DPLNGDAAAM YLHRPEEYKQ KIKEYIQKYA TEEALKEQEE G TGD(SEP)(SEP) ...String: MSSPSPGKRR MDTDVVKLIE SKHEVTILGG LNEFVVKFYG PQGTPYEGGV WKVRVDLPDK YPFKSPSIGF MNKIFHPNID EASGTVKLD VINQTWTALY DLTNIFESFL PQLLAYPNPI DPLNGDAAAM YLHRPEEYKQ KIKEYIQKYA TEEALKEQEE G TGD(SEP)(SEP)(SEP)E(SEP) (SEP)M(SEP)DF(SEP)EDEA QDMEL UniProtKB: Ubiquitin-conjugating enzyme E2 H |
-Macromolecule #3: E3 ubiquitin-protein transferase MAEA
Macromolecule | Name: E3 ubiquitin-protein transferase MAEA / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 45.356332 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MAVQESAAQL SMTLKVQEYP TLKVPYETLN KRFRAAQKNI DRETSHVTMV VAELEKTLSG CPAVDSVVSL LDGVVEKLSV LKRKAVESI QAEDESAKLC KRRIEHLKEH SSDQPAAASV WKRKRMDRMM VEHLLRCGYY NTAVKLARQS GIEDLVNIEM F LTAKEVEE ...String: MAVQESAAQL SMTLKVQEYP TLKVPYETLN KRFRAAQKNI DRETSHVTMV VAELEKTLSG CPAVDSVVSL LDGVVEKLSV LKRKAVESI QAEDESAKLC KRRIEHLKEH SSDQPAAASV WKRKRMDRMM VEHLLRCGYY NTAVKLARQS GIEDLVNIEM F LTAKEVEE SLERRETATC LAWCHDNKSR LRKMKSCLEF SLRIQEFIEL IRQNKRLDAV RHARKHFSQA EGSQLDEVRQ AM GMLAFPP DTHISPYKDL LDPARWRMLI QQFRYDNYRL HQLGNNSVFT LTLQAGLSAI KTPQCYKEDG SSKSPDCPVC SRS LNKLAQ PLPMAHCANS RLVCKISGDV MNENNPPMML PNGYVYGYNS LLSIRQDDKV VCPRTKEVFH FSQAEKVYIM UniProtKB: E3 ubiquitin-protein transferase MAEA |
-Macromolecule #4: Ubiquitin
Macromolecule | Name: Ubiquitin / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 8.576831 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG UniProtKB: Polyubiquitin-C |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 68.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |