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- EMDB-9218: Cryo-EM structures and dynamics of substrate-engaged human 26S pr... -
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Basic information
Entry | Database: EMDB / ID: EMD-9218 | ||||||||||||
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Title | Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome | ||||||||||||
![]() | The complete map of state EB of substrate-engaged human proteasome, low pass-filtered to 3 Angstrom without amplitude correction | ||||||||||||
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Function / homology | ![]() 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 / integrator complex / proteasome accessory 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 / integrator complex / proteasome accessory 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 / metal-dependent deubiquitinase activity / protein K63-linked deubiquitination / proteasome regulatory particle, base subcomplex / regulation of endopeptidase activity / hypothalamus gonadotrophin-releasing hormone neuron development / negative regulation of programmed cell death / female meiosis I / 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 / proteasome core complex / Regulation of ornithine decarboxylase (ODC) / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule / Resolution of D-loop Structures through Holliday Junction Intermediates / Cross-presentation of soluble exogenous antigens (endosomes) / fat pad development / Somitogenesis / K63-linked deubiquitinase activity / Impaired BRCA2 binding to RAD51 / immune system process / myofibril / female gonad development / proteasome binding / seminiferous tubule development / regulation of protein catabolic process / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / blastocyst development / transcription factor binding / general transcription initiation factor binding / NF-kappaB binding / endopeptidase activator activity / proteasome assembly / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / polyubiquitin modification-dependent protein binding / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / positive regulation of RNA polymerase II transcription preinitiation complex assembly / mRNA export from nucleus / energy homeostasis / regulation of neuron apoptotic process / regulation of proteasomal protein catabolic process / enzyme regulator activity / ERAD pathway / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / Maturation of protein E / inclusion body / Maturation of protein E / ER Quality Control Compartment (ERQC) / negative regulation of inflammatory response to antigenic stimulus / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / : / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
![]() | Mao YD | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 743 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 61.4 KB 61.4 KB | Display Display | ![]() |
Images | ![]() | 43.8 KB | ||
Others | ![]() ![]() | 749.7 MB 731 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 527.3 KB | Display | ![]() |
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Full document | ![]() | 526.9 KB | Display | |
Data in XML | ![]() | 7.8 KB | Display | |
Data in CIF | ![]() | 9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6mseMC ![]() 9215C ![]() 9216C ![]() 9217C ![]() 9219C ![]() 9220C ![]() 9221C ![]() 9222C ![]() 9223C ![]() 9224C ![]() 9225C ![]() 9226C ![]() 9227C ![]() 9228C ![]() 9229C ![]() 6msbC ![]() 6msdC ![]() 6msgC ![]() 6mshC ![]() 6msjC ![]() 6mskC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | |
EM raw data | ![]() 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]) |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | The complete map of state EB 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 EB of substrate-engaged...
File | emd_9218_additional_1.map | ||||||||||||
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Annotation | The complete map of state EB of substrate-engaged human proteasome, low pass-filtered to 3 Angstrom with amplitude correction with a B-factor of -35 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Unfiltered, uncorrected raw EB map of complete holoenzyme
File | emd_9218_additional_2.map | ||||||||||||
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Annotation | Unfiltered, uncorrected raw EB 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: 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: substrate
+Macromolecule #21: Proteasome subunit alpha type-6
+Macromolecule #22: Proteasome subunit alpha type-2
+Macromolecule #23: Proteasome subunit alpha type-4
+Macromolecule #24: Proteasome subunit alpha type-7
+Macromolecule #25: Proteasome subunit alpha type-5
+Macromolecule #26: Proteasome subunit alpha type-1
+Macromolecule #27: Proteasome subunit alpha type-3
+Macromolecule #28: Proteasome subunit beta type-6
+Macromolecule #29: Proteasome subunit beta type-7
+Macromolecule #30: Proteasome subunit beta type-3
+Macromolecule #31: Proteasome subunit beta type-2
+Macromolecule #32: Proteasome subunit beta type-5
+Macromolecule #33: Proteasome subunit beta type-1
+Macromolecule #34: Proteasome subunit beta type-4
+Macromolecule #35: ZINC ION
+Macromolecule #36: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #37: MAGNESIUM ION
+Macromolecule #38: ADENOSINE-5'-DIPHOSPHATE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | 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: ![]() |
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
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 242965 |
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Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: PROJECTION MATCHING |