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Yorodumi- EMDB-9216: Cryo-EM structures and dynamics of substrate-engaged human 26S pr... -
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Basic information
| Entry | Database: EMDB / ID: EMD-9216 | ||||||||||||
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| Title | Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome | ||||||||||||
Map data | The complete map of state EA1 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 informationthyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / positive regulation of inclusion body assembly / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex / proteasome regulatory particle ...thyrotropin-releasing hormone receptor binding / nuclear proteasome complex / host-mediated perturbation of viral transcription / positive regulation of inclusion body assembly / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex / proteasome regulatory particle / CD8-positive, alpha-beta T cell differentiation / thymic T cell selection / CD8-positive, alpha-beta T cell homeostasis / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / hypothalamus gonadotrophin-releasing hormone neuron development / proteasome-activating activity / Antigen processing: Ub, ATP-independent proteasomal degradation / female meiosis I / proteasome regulatory particle, lid subcomplex / proteasome regulatory particle, base subcomplex / seminiferous tubule development / positive regulation of protein monoubiquitination / fat pad development / negative regulation of regulatory T cell differentiation / mitochondrion transport along microtubule / T-helper 1 cell differentiation / protein K63-linked deubiquitination / metal-dependent deubiquitinase activity / cellular response to type I interferon / negative regulation of programmed cell death / Regulation of ornithine decarboxylase (ODC) / proteasome core complex / Proteasome assembly / T-helper 17 cell differentiation / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / Cross-presentation of soluble exogenous antigens (endosomes) / transcription factor binding / K63-linked deubiquitinase activity / Somitogenesis / flagellated sperm motility / 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) / female gonad development / Resolution of D-loop Structures through Holliday Junction Intermediates / proteasome binding / Impaired BRCA2 binding to RAD51 / myofibril / male meiosis I / positive regulation of RNA polymerase II transcription preinitiation complex assembly / proteasomal ubiquitin-independent protein catabolic process / general transcription initiation factor binding / Presynaptic phase of homologous DNA pairing and strand exchange / proteasome storage granule / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) / protein deubiquitination / polyubiquitin modification-dependent protein binding / proteasome endopeptidase complex / NF-kappaB binding / proteasome core complex, beta-subunit complex / endopeptidase activator activity / energy homeostasis / threonine-type endopeptidase activity / GSK3B-mediated proteasomal degradation of PD-L1(CD274) / proteasome core complex, alpha-subunit complex / SPOP-mediated proteasomal degradation of PD-L1(CD274) / proteasome assembly / mRNA export from nucleus / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / immune system process / regulation of G1/S transition of mitotic cell cycle / regulation of macroautophagy / enzyme regulator activity / Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide / neuron projection morphogenesis / positive regulation of interleukin-2 production / ciliary tip / ERAD pathway / response to type II interferon / inclusion body / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / regulation of neuron apoptotic process / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / 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 / Prevention of phagosomal-lysosomal fusion / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.0 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_9216.map.gz | 746.9 MB | EMDB map data format | |
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| Header (meta data) | emd-9216-v30.xml emd-9216.xml | 69.3 KB 69.3 KB | Display Display | EMDB header |
| Images | emd_9216.png | 48.5 KB | ||
| Filedesc metadata | emd-9216.cif.gz | 15.9 KB | ||
| Others | emd_9216_additional_1.map.gz emd_9216_additional_2.map.gz | 730.7 MB 755 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9216 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9216 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 6msbMC ![]() 9215C ![]() 9217C ![]() 9218C ![]() 9219C ![]() 9220C ![]() 9221C ![]() 9222C ![]() 9223C ![]() 9224C ![]() 9225C ![]() 9226C ![]() 9227C ![]() 9228C ![]() 9229C ![]() 6msdC ![]() 6mseC ![]() 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 | 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_9216.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 EA1 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 EA1 map of complete holoenzyme
| File | emd_9216_additional_1.map | ||||||||||||
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| Annotation | Unfiltered, uncorrected raw EA1 map of complete holoenzyme | ||||||||||||
| Projections & Slices |
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| Density Histograms |
-Additional map: The complete map of state EA1 of substrate-engaged...
| File | emd_9216_additional_2.map | ||||||||||||
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| Annotation | The complete map of state EA1 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 |
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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 |
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Sample preparation
| Buffer | pH: 8 |
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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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About Yorodumi


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






















































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Y (Row.)
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Processing
