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Yorodumi- EMDB-9217: Cryo-EM structures and dynamics of substrate-engaged human 26S pr... -
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-Basic information
Entry | Database: EMDB / ID: EMD-9217 | ||||||||||||
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Title | Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome | ||||||||||||
Map data | The complete map of state EA2 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 / meiosis I / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex ...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 / meiosis I / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex / proteasome regulatory particle / positive regulation of proteasomal protein catabolic process / cytosolic proteasome complex / proteasome regulatory particle, lid subcomplex / negative regulation of programmed cell death / proteasome-activating activity / proteasome regulatory particle, base subcomplex / metal-dependent deubiquitinase activity / regulation of endopeptidase activity / protein K63-linked deubiquitination / hypothalamus gonadotrophin-releasing hormone neuron development / Regulation of ornithine decarboxylase (ODC) / 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) / proteasome core complex / female meiosis I / positive regulation of protein monoubiquitination / Resolution of D-loop Structures through Holliday Junction Intermediates / Cross-presentation of soluble exogenous antigens (endosomes) / mitochondrion transport along microtubule / fat pad development / K63-linked deubiquitinase activity / Somitogenesis / : / Impaired BRCA2 binding to RAD51 / immune system process / myofibril / proteasome binding / female gonad development / regulation of protein catabolic process / seminiferous tubule development / transcription factor binding / male meiosis I / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / blastocyst development / general transcription initiation factor binding / polyubiquitin modification-dependent protein binding / NF-kappaB binding / endopeptidase activator activity / 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 neuron apoptotic process / mRNA export from nucleus / enzyme regulator activity / regulation of proteasomal protein catabolic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of inflammatory response to antigenic stimulus / ERAD pathway / energy homeostasis / inclusion body / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / FLT3 signaling by CBL mutants / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Glycogen synthesis / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / TICAM1,TRAF6-dependent induction of TAK1 complex / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of FZD by ubiquitination / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / p75NTR recruits signalling complexes / APC/C:Cdc20 mediated degradation of Cyclin B / VLDLR internalisation and degradation / Downregulation of ERBB4 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / sarcomere 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: 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_9217.map.gz | 748.5 MB | EMDB map data format | |
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Header (meta data) | emd-9217-v30.xml emd-9217.xml | 60.8 KB 60.8 KB | Display Display | EMDB header |
Images | emd_9217.png | 37.6 KB | ||
Others | emd_9217_additional_1.map.gz emd_9217_additional_2.map.gz | 731.4 MB 756.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9217 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9217 | HTTPS FTP |
-Validation report
Summary document | emd_9217_validation.pdf.gz | 544.7 KB | Display | EMDB validaton report |
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Full document | emd_9217_full_validation.pdf.gz | 544.2 KB | Display | |
Data in XML | emd_9217_validation.xml.gz | 7.7 KB | Display | |
Data in CIF | emd_9217_validation.cif.gz | 9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9217 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9217 | HTTPS FTP |
-Related structure data
Related structure data | 6msdMC 9215C 9216C 9218C 9219C 9220C 9221C 9222C 9223C 9224C 9225C 9226C 9227C 9228C 9229C 6msbC 6mseC 6msgC 6mshC 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_9217.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 EA2 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: Unfiltered, uncorrected raw EA2 map of complete holoenzyme
File | emd_9217_additional_1.map | ||||||||||||
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Annotation | Unfiltered, uncorrected raw EA2 map of complete holoenzyme | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: The complete map of state EA2 of substrate-engaged...
File | emd_9217_additional_2.map | ||||||||||||
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Annotation | The complete map of state EA2 of substrate-engaged human proteasome, low pass-filtered to 3.2 Angstrom with amplitude correction with a B-factor of -46 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Human 26S proteasome
+Supramolecule #1: Human 26S 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: Ubiquitin
+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 |
-Sample preparation
Buffer | pH: 8 |
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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 | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 79691 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: PROJECTION MATCHING |