[English] 日本語
Yorodumi- EMDB-65839: Structure of human 26S proteasome complexed with midnolin, 19S pr... -
+
Open data
-
Basic information
| Entry | ![]() | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Title | Structure of human 26S proteasome complexed with midnolin, 19S proteasome with Ubl and Catch domain resolved | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | 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 / integrator complex / proteasome regulatory particle ...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 / integrator complex / proteasome regulatory particle / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / transcription factor binding / proteasome-activating activity / proteasome regulatory particle, lid subcomplex / proteasome regulatory particle, base subcomplex / negative regulation of programmed cell death / protein K63-linked deubiquitination / metal-dependent deubiquitinase activity / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / cellular response to type I interferon / 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) / Resolution of D-loop Structures through Holliday Junction Intermediates / detection of maltose stimulus / proteasome binding / carbohydrate transport / Impaired BRCA2 binding to RAD51 / negative regulation of insulin secretion / proteasomal ubiquitin-independent protein catabolic process / positive regulation of RNA polymerase II transcription preinitiation complex assembly / general transcription initiation factor binding / carbohydrate transmembrane transporter activity / proteasome storage granule / maltose binding / Presynaptic phase of homologous DNA pairing and strand exchange / maltose transport / maltodextrin transmembrane transport / polyubiquitin modification-dependent protein binding / protein deubiquitination / endopeptidase activator activity / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / proteasome assembly / mRNA export from nucleus / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / regulation of macroautophagy / stem cell differentiation / proteasome complex / enzyme regulator activity / ERAD pathway / ATP-binding cassette (ABC) transporter complex / inclusion body / TBP-class protein binding / regulation of proteasomal protein catabolic process / cell chemotaxis / Regulation of activated PAK-2p34 by proteasome mediated degradation / ubiquitin binding / 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 / 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 / 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 / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / G2/M Checkpoints / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / Autodegradation of the E3 ubiquitin ligase COP1 / Regulation of RUNX3 expression and activity / double-strand break repair via homologous recombination / Defective CFTR causes cystic fibrosis / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) / Hedgehog 'on' state / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Vif-mediated degradation of APOBEC3G / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of GLI2 by the proteasome Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / Pseudotamlana agarivorans (bacteria) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 4.23 Å | |||||||||
Authors | Zhu C / Qin L / Liang L | |||||||||
| Funding support | China, 1 items
| |||||||||
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. | |||||||||
| History |
|
-
Structure visualization
| Supplemental images |
|---|
-
Downloads & links
-EMDB archive
| Map data | emd_65839.map.gz | 121.5 MB | EMDB map data format | |
|---|---|---|---|---|
| Header (meta data) | emd-65839-v30.xml emd-65839.xml | 43.1 KB 43.1 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_65839_fsc.xml | 13.2 KB | Display | FSC data file |
| Images | emd_65839.png | 53.3 KB | ||
| Filedesc metadata | emd-65839.cif.gz | 12.4 KB | ||
| Others | emd_65839_half_map_1.map.gz emd_65839_half_map_2.map.gz | 226.9 MB 226.9 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-65839 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-65839 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9wbgMC ![]() 22mmC ![]() 9mboC ![]() 9mbpC ![]() 9mbqC ![]() 9u3lC ![]() 9u4mC ![]() 9u7rC ![]() 9w39C M: atomic model generated by this map C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| Related items in Molecule of the Month |
-
Map
| File | Download / File: emd_65839.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||||||||||||||||||
| Density |
| ||||||||||||||||||||||||||||||||||||
| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
|
-Supplemental data
-Half map: #1
| File | emd_65839_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Half map: #2
| File | emd_65839_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-
Sample components
+Entire : 26S proteasome complex with midnolin
+Supramolecule #1: 26S proteasome complex with midnolin
+Macromolecule #1: Maltose/maltodextrin-binding periplasmic protein,Midnolin
+Macromolecule #2: 26S proteasome regulatory subunit 8
+Macromolecule #3: 26S proteasome regulatory subunit 6B
+Macromolecule #4: 26S proteasome non-ATPase regulatory subunit 3
+Macromolecule #5: 26S proteasome non-ATPase regulatory subunit 12
+Macromolecule #6: 26S proteasome non-ATPase regulatory subunit 11
+Macromolecule #7: 26S proteasome non-ATPase regulatory subunit 6
+Macromolecule #8: 26S proteasome non-ATPase regulatory subunit 7
+Macromolecule #9: 26S proteasome non-ATPase regulatory subunit 13
+Macromolecule #10: 26S proteasome non-ATPase regulatory subunit 4
+Macromolecule #11: 26S proteasome non-ATPase regulatory subunit 8
+Macromolecule #12: 26S proteasome complex subunit SEM1
+Macromolecule #13: Substrate
+Macromolecule #14: 26S proteasome non-ATPase regulatory subunit 1
+Macromolecule #15: Ubiquitin C-terminal hydrolase PSMD14,Uncharacterized protein
+Macromolecule #16: 26S proteasome regulatory subunit 7
+Macromolecule #17: 26S proteasome regulatory subunit 4
+Macromolecule #18: 26S proteasome regulatory subunit 10B
+Macromolecule #19: 26S proteasome regulatory subunit 6A
+Macromolecule #20: Early growth response protein 1
+Macromolecule #21: ADENOSINE-5'-DIPHOSPHATE
+Macromolecule #22: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #23: ZINC ION
+Macromolecule #24: MAGNESIUM ION
-Experimental details
-Structure determination
| Method | cryo EM |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Buffer | pH: 7.4 |
|---|---|
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
| Microscope | TFS KRIOS |
|---|---|
| Image recording | Film or detector model: GATAN K3 (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 |
Movie
Controller
About Yorodumi



Keywords
Homo sapiens (human)
Pseudotamlana agarivorans (bacteria)
Authors
China, 1 items
Citation






































Z (Sec.)
Y (Row.)
X (Col.)






































Processing
FIELD EMISSION GUN

