+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4002 | |||||||||
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Title | The human 26S proteasome at 3.9 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information positive regulation of inclusion body assembly / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / proteasome accessory complex / meiosis I / positive regulation of proteasomal protein catabolic process / metal-dependent deubiquitinase activity ...positive regulation of inclusion body assembly / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / proteasome accessory complex / meiosis I / positive regulation of proteasomal protein catabolic process / metal-dependent deubiquitinase activity / proteasome regulatory particle / purine ribonucleoside triphosphate binding / cytosolic proteasome complex / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / protein K63-linked deubiquitination / negative regulation of programmed cell death / regulation of endopeptidase activity / 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 / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / Resolution of D-loop Structures through Holliday Junction Intermediates / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / Impaired BRCA2 binding to RAD51 / K63-linked deubiquitinase activity / immune system process / myofibril / proteasome binding / regulation of protein catabolic process / Presynaptic phase of homologous DNA pairing and strand exchange / proteasome storage granule / blastocyst development / transcription factor binding / polyubiquitin modification-dependent protein binding / general transcription initiation factor binding / endopeptidase activator activity / NF-kappaB binding / proteasome assembly / positive regulation of RNA polymerase II transcription preinitiation complex assembly / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / regulation of proteasomal protein catabolic process / enzyme regulator activity / mRNA export from nucleus / : / inclusion body / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of inflammatory response to antigenic stimulus / response to organonitrogen compound / proteolysis involved in protein catabolic process / proteasome complex / sarcomere / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Degradation of DVL / proteasomal protein catabolic process / P-body / stem cell differentiation / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Dectin-1 mediated noncanonical NF-kB signaling / Hh mutants are degraded by ERAD / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Degradation of AXIN / Defective CFTR causes cystic fibrosis / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / lipopolysaccharide binding / Hedgehog ligand biogenesis / Negative regulation of NOTCH4 signaling / double-strand break repair via homologous recombination / G2/M Checkpoints / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Autodegradation of the E3 ubiquitin ligase COP1 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / Regulation of RUNX3 expression and activity / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / response to virus Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Schweitzer A / Aufderheide A / Rudack T / Beck F | |||||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2016 Title: Structure of the human 26S proteasome at a resolution of 3.9 Å. Authors: Andreas Schweitzer / Antje Aufderheide / Till Rudack / Florian Beck / Günter Pfeifer / Jürgen M Plitzko / Eri Sakata / Klaus Schulten / Friedrich Förster / Wolfgang Baumeister / Abstract: Protein degradation in eukaryotic cells is performed by the Ubiquitin-Proteasome System (UPS). The 26S proteasome holocomplex consists of a core particle (CP) that proteolytically degrades ...Protein degradation in eukaryotic cells is performed by the Ubiquitin-Proteasome System (UPS). The 26S proteasome holocomplex consists of a core particle (CP) that proteolytically degrades polyubiquitylated proteins, and a regulatory particle (RP) containing the AAA-ATPase module. This module controls access to the proteolytic chamber inside the CP and is surrounded by non-ATPase subunits (Rpns) that recognize substrates and deubiquitylate them before unfolding and degradation. The architecture of the 26S holocomplex is highly conserved between yeast and humans. The structure of the human 26S holocomplex described here reveals previously unidentified features of the AAA-ATPase heterohexamer. One subunit, Rpt6, has ADP bound, whereas the other five have ATP in their binding pockets. Rpt6 is structurally distinct from the other five Rpt subunits, most notably in its pore loop region. For Rpns, the map reveals two main, previously undetected, features: the C terminus of Rpn3 protrudes into the mouth of the ATPase ring; and Rpn1 and Rpn2, the largest proteasome subunits, are linked by an extended connection. The structural features of the 26S proteasome observed in this study are likely to be important for coordinating the proteasomal subunits during substrate processing. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4002.map.gz | 14.6 MB | EMDB map data format | |
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Header (meta data) | emd-4002-v30.xml emd-4002.xml | 10.5 KB 10.5 KB | Display Display | EMDB header |
Images | emd_4002.png | 138.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4002 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4002 | HTTPS FTP |
-Related structure data
Related structure data | 5l4gMC 5l4kMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4002.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Human 26S proteasome
Entire | Name: Human 26S proteasomeProteasome |
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Components |
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-Supramolecule #1: Human 26S proteasome
Supramolecule | Name: Human 26S proteasome / type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 2.5 MDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | cell |
-Sample preparation
Concentration | 0.5 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R2/1 / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: HOMEMADE PLUNGER |
Details | This sample was monodisperse. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.3 mm / Nominal defocus min: 1.9 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: OTHER / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number grids imaged: 19 / Number real images: 40211 / Average exposure time: 1.5 sec. / Average electron dose: 45.0 e/Å2 Details: Images were collected in movie-mode at 33 frames/s. |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 688742 |
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CTF correction | Software - Name: CTFFIND (ver. 4.0) |
Startup model | Type of model: EMDB MAP EMDB ID: |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 1.4) / Number images used: 461402 |
Details | Falcon III |