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Yorodumi- EMDB-9220: Cryo-EM structures and dynamics of substrate-engaged human 26S pr... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9220 | ||||||||||||
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Title | Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome | ||||||||||||
Map data | The complete map of state EC2 of substrate-engaged human proteasome, low pass-filtered to 3 Angstrom without amplitude correction | ||||||||||||
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 / integrator complex / purine ribonucleoside triphosphate binding / meiosis I ...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 / integrator complex / purine ribonucleoside triphosphate binding / meiosis I / positive regulation of proteasomal protein catabolic process / proteasome regulatory particle / cytosolic proteasome complex / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / protein K63-linked deubiquitination / metal-dependent deubiquitinase activity / regulation of endopeptidase activity / negative regulation of programmed cell death / 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 / Regulation of ornithine decarboxylase (ODC) / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / proteasome core complex / Resolution of D-loop Structures through Holliday Junction Intermediates / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / K63-linked deubiquitinase activity / Impaired BRCA2 binding to RAD51 / immune system process / myofibril / proteasome binding / regulation of protein catabolic process / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / transcription factor binding / blastocyst development / general transcription initiation factor binding / NF-kappaB binding / endopeptidase activator activity / polyubiquitin modification-dependent protein binding / proteasome assembly / proteasome endopeptidase complex / positive regulation of RNA polymerase II transcription preinitiation complex assembly / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / mRNA export from nucleus / enzyme regulator activity / regulation of proteasomal protein catabolic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / ERAD pathway / inclusion body / negative regulation of inflammatory response to antigenic stimulus / : / sarcomere / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / proteolysis involved in protein catabolic process / 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 / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Degradation of DVL / stem cell differentiation / CDK-mediated phosphorylation and removal of Cdc6 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Hh mutants are degraded by ERAD / lipopolysaccharide binding / SCF(Skp2)-mediated degradation of p27/p21 / Degradation of AXIN / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / G2/M Checkpoints / Vif-mediated degradation of APOBEC3G / Autodegradation of the E3 ubiquitin ligase COP1 / Hedgehog 'on' state / Regulation of RUNX3 expression and activity / P-body / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Orc1 removal from chromatin / double-strand break repair via homologous recombination Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Saccharomyces cerevisiae RM11-1a (yeast) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||||||||
Authors | Mao YD | ||||||||||||
Funding support | China, United States, 3 items
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Citation | Journal: Nature / Year: 2019 Title: Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome. Authors: Yuanchen Dong / Shuwen Zhang / Zhaolong Wu / Xuemei Li / Wei Li Wang / Yanan Zhu / Svetla Stoilova-McPhie / Ying Lu / Daniel Finley / Youdong Mao / Abstract: The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of ...The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate. | ||||||||||||
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_9220.map.gz | 748.3 MB | EMDB map data format | |
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Header (meta data) | emd-9220-v30.xml emd-9220.xml | 60.1 KB 60.1 KB | Display Display | EMDB header |
Images | emd_9220.png | 99.6 KB | ||
Others | emd_9220_additional_1.map.gz emd_9220_additional_2.map.gz | 751.1 MB 731.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9220 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9220 | HTTPS FTP |
-Validation report
Summary document | emd_9220_validation.pdf.gz | 562.9 KB | Display | EMDB validaton report |
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Full document | emd_9220_full_validation.pdf.gz | 562.4 KB | Display | |
Data in XML | emd_9220_validation.xml.gz | 7.8 KB | Display | |
Data in CIF | emd_9220_validation.cif.gz | 9.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9220 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9220 | HTTPS FTP |
-Related structure data
Related structure data | 6mshMC 9215C 9216C 9217C 9218C 9219C 9221C 9222C 9223C 9224C 9225C 9226C 9227C 9228C 9229C 6msbC 6msdC 6mseC 6msgC 6msjC 6mskC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | |
EM raw data | EMPIAR-10669 (Title: Cryo-EM dataset of the substrate-engaged human 26S proteasome Data size: 13.9 TB Data #1: Drift-corrected frame-averaged super-counting mode micrographs and extracted particles of substrate-engaged human 26S proteasome [micrographs - single frame]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9220.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | The complete map of state EC2 of substrate-engaged human proteasome, low pass-filtered to 3 Angstrom without amplitude correction | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.685 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: The complete map of state EC2 of substrate-engaged...
File | emd_9220_additional_1.map | ||||||||||||
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Annotation | The complete map of state EC2 of substrate-engaged human proteasome, low pass-filtered to 3.5 Angstrom with amplitude correction with a B-factor of -30 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Unfiltered, uncorrected raw EC2 map of complete holoenzyme
File | emd_9220_additional_2.map | ||||||||||||
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Annotation | Unfiltered, uncorrected raw EC2 map of complete holoenzyme | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Proteasome
+Supramolecule #1: Proteasome
+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 4
+Macromolecule #9: 26S proteasome non-ATPase regulatory subunit 14
+Macromolecule #10: 26S proteasome non-ATPase regulatory subunit 8
+Macromolecule #11: 26S proteasome complex subunit SEM1
+Macromolecule #12: 26S proteasome non-ATPase regulatory subunit 2
+Macromolecule #13: 26S proteasome regulatory subunit 7
+Macromolecule #14: 26S proteasome regulatory subunit 4
+Macromolecule #15: 26S proteasome regulatory subunit 8
+Macromolecule #16: 26S proteasome regulatory subunit 6B
+Macromolecule #17: 26S proteasome regulatory subunit 10B
+Macromolecule #18: 26S proteasome regulatory subunit 6A
+Macromolecule #19: substrate
+Macromolecule #20: Proteasome subunit alpha type-6
+Macromolecule #21: Proteasome subunit alpha type-2
+Macromolecule #22: Proteasome subunit alpha type-4
+Macromolecule #23: Proteasome subunit alpha type-7
+Macromolecule #24: Proteasome subunit alpha type-5
+Macromolecule #25: Proteasome subunit alpha type-1
+Macromolecule #26: Proteasome subunit alpha type-3
+Macromolecule #27: Proteasome subunit beta type-6
+Macromolecule #28: Proteasome subunit beta type-7
+Macromolecule #29: Proteasome subunit beta type-3
+Macromolecule #30: Proteasome subunit beta type-2
+Macromolecule #31: Proteasome subunit beta type-5
+Macromolecule #32: Proteasome subunit beta type-1
+Macromolecule #33: Proteasome subunit beta type-4
+Macromolecule #34: ZINC ION
+Macromolecule #35: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #36: ADENOSINE-5'-DIPHOSPHATE
-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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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 44.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 71651 |
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Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: PROJECTION MATCHING |