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Yorodumi- EMDB-42506: Non-substrate-engaged human 26S proteasome with Nub1/FAT10 bound ... -
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Basic information
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| Title | Non-substrate-engaged human 26S proteasome with Nub1/FAT10 bound to Rpn1 | |||||||||
Map data | human 26S proteasome, 19S complex bound to UBL of Nub1. | |||||||||
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Keywords | 26S protease complex / Nub1 / FAT10 / MOTOR PROTEIN / HYDROLASE-PROTEIN BINDING complex | |||||||||
| Function / homology | Function and homology informationregulation of ubiquitin-dependent protein catabolic process / positive regulation of inclusion body assembly / thyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex ...regulation of ubiquitin-dependent protein catabolic process / positive regulation of inclusion body assembly / thyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex / proteasome regulatory particle / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / CD8-positive, alpha-beta T cell differentiation / CD8-positive, alpha-beta T cell homeostasis / transcription factor binding / thymic T cell selection / Antigen processing: Ub, ATP-independent proteasomal degradation / proteasome-activating activity / proteasome regulatory particle, lid subcomplex / proteasome regulatory particle, base subcomplex / negative regulation of programmed cell death / negative regulation of regulatory T cell differentiation / T-helper 1 cell differentiation / protein K63-linked deubiquitination / metal-dependent deubiquitinase activity / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / Proteasome assembly / cellular response to type I interferon / T-helper 17 cell differentiation / Cross-presentation of soluble exogenous antigens (endosomes) / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / Somitogenesis / K63-linked deubiquitinase activity / Homologous DNA Pairing and Strand Exchange / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / flagellated sperm motility / Resolution of D-loop Structures through Holliday Junction Intermediates / sperm end piece / Lewy body / proteasome binding / Impaired BRCA2 binding to RAD51 / myofibril / ciliary tip / response to tumor necrosis factor / proteasomal ubiquitin-independent protein catabolic process / positive regulation of RNA polymerase II transcription preinitiation complex assembly / general transcription initiation factor binding / Presynaptic phase of homologous DNA pairing and strand exchange / proteasome storage granule / polyubiquitin modification-dependent protein binding / proteasome endopeptidase complex / protein deubiquitination / NF-kappaB binding / proteasome core complex, beta-subunit complex / endopeptidase activator activity / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / proteasome assembly / mRNA export from nucleus / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / immune system process / regulation of G1/S transition of mitotic cell cycle / stem cell differentiation / regulation of macroautophagy / positive regulation of interleukin-2 production / proteasome complex / enzyme regulator activity / ERAD pathway / response to type II interferon / inclusion body / TBP-class protein binding / : / regulation of proteasomal protein catabolic process / sarcomere / Regulation of activated PAK-2p34 by proteasome mediated degradation / ubiquitin binding / negative regulation of inflammatory response to antigenic stimulus / Autodegradation of Cdh1 by Cdh1:APC/C / proteasomal protein catabolic process / APC/C:Cdc20 mediated degradation of Securin / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / lipopolysaccharide binding / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / positive regulation of type II interferon production / Assembly of the pre-replicative complex / P-body / Vpu mediated degradation of CD4 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of DVL Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.73 Å | |||||||||
Authors | Arkinson C / Gee CL / Martin A | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2025Title: NUB1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome. Authors: Connor Arkinson / Ken C Dong / Christine L Gee / Shawn M Costello / Aimee Chi Soe / Greg L Hura / Susan Marqusee / Andreas Martin / ![]() Abstract: The ubiquitin-like modifier FAT10 targets hundreds of proteins in the mammalian immune system to the 26S proteasome for degradation. This degradation pathway requires the cofactor NUB1, yet the ...The ubiquitin-like modifier FAT10 targets hundreds of proteins in the mammalian immune system to the 26S proteasome for degradation. This degradation pathway requires the cofactor NUB1, yet the underlying mechanisms remain unknown. Here, we reconstituted a minimal in vitro system with human components and revealed that NUB1 uses the intrinsic instability of FAT10 to trap its N-terminal ubiquitin-like domain in an unfolded state and deliver it to the 26S proteasome for engagement, allowing the degradation of FAT10-ylated substrates in a ubiquitin-independent and p97-independent manner. Using hydrogen-deuterium exchange, structural modeling and site-directed mutagenesis, we identified the formation of an intricate complex with FAT10 that activates NUB1 for docking to the 26S proteasome, and our cryo-EM studies visualized the highly dynamic NUB1 complex bound to the proteasomal Rpn1 subunit during FAT10 delivery and the early stages of ATP-dependent degradation. These findings identified a previously unknown mode of cofactor-mediated, ubiquitin-independent substrate delivery to the 26S proteasome that relies on trapping partially unfolded states for engagement by the proteasomal ATPase motor. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_42506.map.gz | 42.5 MB | EMDB map data format | |
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| Header (meta data) | emd-42506-v30.xml emd-42506.xml | 53 KB 53 KB | Display Display | EMDB header |
| Images | emd_42506.png | 96.3 KB | ||
| Filedesc metadata | emd-42506.cif.gz | 14.6 KB | ||
| Others | emd_42506_half_map_1.map.gz emd_42506_half_map_2.map.gz | 77.8 MB 77.8 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42506 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42506 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8usbMC ![]() 8uscC ![]() 8usdC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_42506.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | human 26S proteasome, 19S complex bound to UBL of Nub1. | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.048 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_42506_half_map_1.map | ||||||||||||
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| Projections & Slices |
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| Density Histograms |
-Half map: #1
| File | emd_42506_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
+Entire : 26S proteasome complex bound to Nub1
+Supramolecule #1: 26S proteasome complex bound to Nub1
+Supramolecule #2: Nub1 UBL1
+Macromolecule #1: 26S proteasome non-ATPase regulatory subunit 12
+Macromolecule #2: 26S protease regulatory subunit 8
+Macromolecule #3: 26S proteasome non-ATPase regulatory subunit 4
+Macromolecule #4: 26S proteasome non-ATPase regulatory subunit 8
+Macromolecule #5: 26S proteasome non-ATPase regulatory subunit 2
+Macromolecule #6: NEDD8 ultimate buster 1
+Macromolecule #7: 26S proteasome regulatory subunit 4
+Macromolecule #8: 26S proteasome regulatory subunit 7
+Macromolecule #9: 26S proteasome regulatory subunit 6B
+Macromolecule #10: 26S protease regulatory subunit 10B
+Macromolecule #11: 26S proteasome regulatory subunit 6A
+Macromolecule #12: Proteasome subunit alpha type-6
+Macromolecule #13: Proteasome subunit alpha type-2
+Macromolecule #14: Proteasome subunit alpha type-4
+Macromolecule #15: Proteasome subunit alpha type-7
+Macromolecule #16: Proteasome subunit alpha type-5
+Macromolecule #17: Proteasome subunit alpha type-1
+Macromolecule #18: Proteasome subunit alpha type-3
+Macromolecule #19: Proteasome subunit beta type-7
+Macromolecule #20: 26S proteasome non-ATPase regulatory subunit 1
+Macromolecule #21: 26S proteasome non-ATPase regulatory subunit 3
+Macromolecule #22: 26S proteasome non-ATPase regulatory subunit 14
+Macromolecule #23: 26S proteasome complex subunit SEM1
+Macromolecule #24: 26S proteasome non-ATPase regulatory subunit 6
+Macromolecule #25: 26S proteasome non-ATPase regulatory subunit 7
+Macromolecule #26: 26S proteasome non-ATPase regulatory subunit 13
+Macromolecule #27: 26S proteasome non-ATPase regulatory subunit 11
+Macromolecule #28: ADENOSINE-5'-DIPHOSPHATE
+Macromolecule #29: MAGNESIUM ION
+Macromolecule #30: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #31: ZINC ION
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 Details: 30 mM HEPES pH7.4, 25 mM NaCl, 25 mM KCl, 3% (v/v) glycerol, 5 mM MgCl2 2 mM ATP and 0.5 mM TCEP |
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| Grid | Model: UltrAuFoil R2/2 / Material: GOLD / Mesh: 500 / Support film - Material: GOLD / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 25 sec. / Details: 25 mA |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 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: 1.7 µm / Nominal defocus min: 0.5 µm |
| Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
United States, 1 items
Citation

















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Processing
FIELD EMISSION GUN
