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Yorodumi- EMDB-9222: Cryo-EM structures and dynamics of substrate-engaged human 26S pr... -
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Basic information
| Entry | Database: EMDB / ID: EMD-9222 | ||||||||||||
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| Title | Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome | ||||||||||||
Map data | The complete map of state ED2 of substrate-engaged human proteasome, low pass-filtered to 3 Angstrom without amplitude correction | ||||||||||||
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Keywords | Proteosome / HYDROLASE | ||||||||||||
| Function / homology | Function and homology informationpositive 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 / cytosolic proteasome complex ...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 / cytosolic proteasome complex / proteasome regulatory particle / structural constituent of proteasome / positive regulation of proteasomal protein catabolic process / transcription factor binding / CD8-positive, alpha-beta T cell differentiation / CD8-positive, alpha-beta T cell homeostasis / thymic T cell selection / Antigen processing: Ub, ATP-independent proteasomal degradation / transcription export complex 2 / proteasome-activating activity / spermatoproteasome complex / proteasome regulatory particle, lid subcomplex / negative regulation of programmed cell death / negative regulation of regulatory T cell differentiation / T-helper 1 cell differentiation / 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 / protein K63-linked deubiquitination / 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 / proteasome binding / sperm end piece / Impaired BRCA2 binding to RAD51 / myofibril / immune system process / proteasomal ubiquitin-independent protein catabolic process / positive regulation of RNA polymerase II transcription preinitiation complex assembly / general transcription initiation factor binding / : / ciliary tip / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / protein deubiquitination / proteasome endopeptidase complex / 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 / proteasome complex / enzyme regulator activity / regulation of G1/S transition of mitotic cell cycle / regulation of macroautophagy / stem cell differentiation / positive regulation of interleukin-2 production / ERAD pathway / response to type II interferon / inclusion body / Activation of STAT3 by cadherin engagement / TBP-class protein binding / regulation of proteasomal protein catabolic process / meiotic cell cycle / sarcomere / Regulation of activated PAK-2p34 by proteasome mediated degradation / ubiquitin binding / negative regulation of inflammatory response to antigenic stimulus / proteasomal protein catabolic process / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / lipopolysaccharide binding / protein catabolic process / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / SCF-beta-TrCP mediated degradation of Emi1 / AUF1 (hnRNP D0) binds and destabilizes mRNA / NIK-->noncanonical NF-kB signaling / positive regulation of type II interferon production / TNFR2 non-canonical NF-kB pathway / P-body / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) / ![]() | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||
Authors | Mao YD | ||||||||||||
| Funding support | China, United States, 3 items
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Citation | Journal: Nature / Year: 2019Title: 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. | ||||||||||||
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Structure visualization
| Movie |
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| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_9222.map.gz | 742.4 MB | EMDB map data format | |
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| Header (meta data) | emd-9222-v30.xml emd-9222.xml | 62.8 KB 62.8 KB | Display Display | EMDB header |
| Images | emd_9222.png | 55 KB | ||
| Filedesc metadata | emd-9222.cif.gz | 14.7 KB | ||
| Others | emd_9222_additional_1.map.gz emd_9222_additional_2.map.gz | 750.2 MB 730.9 MB | ||
| Archive directory | https://data.pdbj.org/pub/emdb/structures/EMD-9222 ftp://data.pdbj.org/pub/emdb/structures/EMD-9222 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 6mskMC ![]() 9215C ![]() 9216C ![]() 9217C ![]() 9218C ![]() 9219C ![]() 9220C ![]() 9221C ![]() 9223C ![]() 9224C ![]() 9225C ![]() 9226C ![]() 9227C ![]() 9228C ![]() 9229C ![]() 6msbC ![]() 6msdC ![]() 6mseC ![]() 6msgC ![]() 6mshC ![]() 6msjC C: citing same article ( 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 proteasomeData 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]) |
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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_9222.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 ED2 of substrate-engaged human proteasome, low pass-filtered to 3 Angstrom without amplitude correction | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 ED2 of substrate-engaged...
| File | emd_9222_additional_1.map | ||||||||||||
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| Annotation | The complete map of state ED2 of substrate-engaged human proteasome, low pass-filtered to 3 Angstrom with amplitude correction with a B-factor of -40 | ||||||||||||
| Projections & Slices |
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| Density Histograms |
-Additional map: Unfiltered, uncorrected raw ED2 map of complete holoenzyme
| File | emd_9222_additional_2.map | ||||||||||||
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| Annotation | Unfiltered, uncorrected raw ED2 map of complete holoenzyme | ||||||||||||
| Projections & Slices |
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| Density Histograms |
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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: Rpt2, NP_002793.2 (26SHA chain B)
+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: MAGNESIUM ION
+Macromolecule #37: ADENOSINE-5'-DIPHOSPHATE
-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: 7.5 |
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| Grid | Details: unspecified |
| Vitrification | Cryogen name: ETHANE |
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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 |
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Image processing
| Startup model | Type of model: NONE |
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| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 348646 |
| Initial angle assignment | Type: COMMON LINE |
| Final angle assignment | Type: PROJECTION MATCHING |
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About Yorodumi


Keywords
Homo sapiens (human)
Authors
China,
United States, 3 items
Citation
UCSF Chimera





































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