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Yorodumi- EMDB-68472: Structure of human 26S proteasome complexed with midnolin(1-111+3... -
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Basic information
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| Title | Structure of human 26S proteasome complexed with midnolin(1-111+337-468) | |||||||||
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Keywords | 26S proteasome / midnolin / HYDROLASE | |||||||||
| Function / homology | Function and homology informationnegative regulation of glucokinase activity / 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 ...negative regulation of glucokinase activity / 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 / proteasome binding / myofibril / Impaired BRCA2 binding to RAD51 / ciliary tip / negative regulation of insulin secretion / proteasomal ubiquitin-independent protein catabolic process / general transcription initiation factor binding / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / 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 / immune system process / regulation of G1/S transition of mitotic cell cycle / regulation of macroautophagy / stem cell differentiation / positive regulation of interleukin-2 production / proteasome complex / enzyme regulator activity / response to type II interferon / inclusion body / TBP-class protein binding / : / regulation of proteasomal protein catabolic process / bioluminescence / sarcomere / Regulation of activated PAK-2p34 by proteasome mediated degradation / generation of precursor metabolites and energy / 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 / lipopolysaccharide binding / Ubiquitin-dependent degradation of Cyclin D / 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 / Degradation of AXIN / Degradation of CRY and PER proteins / meiotic cell cycle Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.42 Å | |||||||||
Authors | Liang L / Zhu C / Qin L | |||||||||
| Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2026Title: Structural dynamics of the midnolin-proteasome during ubiquitin-independent substrate turnover. Authors: Chuanda Zhu / Lu Qin / Zonglin Dai / Peng Zuo / Ao Yang / Lijun Zhong / Zhiqiang Lin / Ling Liang / ![]() Abstract: The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein ...The 26S proteasome typically degrades proteins marked by ubiquitin chains. However, a distinct, ubiquitin-independent degradation pathway for nuclear proteins exists, mediated by the adaptor protein midnolin, yet its molecular mechanism remains poorly understood. Here, we present nine cryo-electron microscopy structures of the human 26S proteasome in complex with midnolin, which collectively delineate a near-complete catalytic cycle. Our structures reveal that midnolin binds to the proteasome via the RPN1 subunit by its C-terminal helix. Unexpectedly, its ubiquitin-like domain interacts with the RPN11 deubiquitinase in a non-catalytic role. This interaction positions the adjacent Catch domain, which is responsible for substrate binding, directly above the proteasomal entrance, potentially facilitating substrate entry into the proteasome. Furthermore, we observe four consecutive spiral staircase conformations of the AAA+ ATPase hexamer during substrate translocation. These findings provide insights into the mechanisms underlying ubiquitin-independent nuclear protein degradation and may help develop strategies for targeting nuclear proteins via direct proteasomal degradation. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_68472.map.gz | 504.4 MB | EMDB map data format | |
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| Header (meta data) | emd-68472-v30.xml emd-68472.xml | 58.5 KB 58.5 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_68472_fsc.xml | 19.9 KB | Display | FSC data file |
| Images | emd_68472.png | 54.6 KB | ||
| Filedesc metadata | emd-68472.cif.gz | 15 KB | ||
| Others | emd_68472_half_map_1.map.gz emd_68472_half_map_2.map.gz | 764.8 MB 764.9 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-68472 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-68472 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 22mmMC ![]() 9mboC ![]() 9mbpC ![]() 9mbqC ![]() 9u3lC ![]() 9u4mC ![]() 9u7rC ![]() 9w39C ![]() 9wbgC 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_68472.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_68472_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #1
| File | emd_68472_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
+Entire : 26S proteasome complexed with midnolin delCatch
+Supramolecule #1: 26S proteasome complexed with midnolin delCatch
+Macromolecule #1: 26S proteasome non-ATPase regulatory subunit 1
+Macromolecule #2: 26S proteasome non-ATPase regulatory subunit 3
+Macromolecule #3: 26S proteasome non-ATPase regulatory subunit 12
+Macromolecule #4: 26S proteasome non-ATPase regulatory subunit 11
+Macromolecule #5: 26S proteasome non-ATPase regulatory subunit 6
+Macromolecule #6: 26S proteasome non-ATPase regulatory subunit 7
+Macromolecule #7: 26S proteasome non-ATPase regulatory subunit 13
+Macromolecule #8: 26S proteasome non-ATPase regulatory subunit 14
+Macromolecule #9: 26S proteasome non-ATPase regulatory subunit 8
+Macromolecule #10: 26S proteasome complex subunit SEM1
+Macromolecule #11: 26S proteasome regulatory subunit 7
+Macromolecule #12: 26S proteasome regulatory subunit 4
+Macromolecule #13: 26S proteasome regulatory subunit 8
+Macromolecule #14: 26S proteasome regulatory subunit 6B
+Macromolecule #15: Proteasome 26S subunit, ATPase 6
+Macromolecule #16: 26S proteasome regulatory subunit 6A
+Macromolecule #17: Proteasome subunit alpha type-6
+Macromolecule #18: Proteasome subunit alpha type-2
+Macromolecule #19: Proteasome subunit alpha type-4
+Macromolecule #20: Proteasome subunit alpha type-7
+Macromolecule #21: Proteasome subunit alpha type-5
+Macromolecule #22: Isoform Long of Proteasome subunit alpha type-1
+Macromolecule #23: Proteasome subunit alpha type-3
+Macromolecule #24: Proteasome subunit beta type-6
+Macromolecule #25: Proteasome subunit beta type-7
+Macromolecule #26: Proteasome subunit beta type-3
+Macromolecule #27: Proteasome subunit beta type-2
+Macromolecule #28: Proteasome subunit beta type-5
+Macromolecule #29: Proteasome subunit beta type-1
+Macromolecule #30: Proteasome subunit beta type-4
+Macromolecule #31: Proteasome subunit alpha type-7
+Macromolecule #32: Midnolin,MCHERRY,fusion tag
+Macromolecule #33: 26S proteasome non-ATPase regulatory subunit 2
+Macromolecule #34: ZINC ION
+Macromolecule #35: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #36: MAGNESIUM ION
+Macromolecule #37: ADENOSINE-5'-DIPHOSPHATE
+Macromolecule #38: N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-4-methyl-1-oxopentan-2-y...
-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 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 40.0 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: 1.8 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
China, 1 items
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Processing
FIELD EMISSION GUN

