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Yorodumi- PDB-5t0j: Structural basis for dynamic regulation of the human 26S proteasome -
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-Basic information
Entry | Database: PDB / ID: 5t0j | ||||||
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Title | Structural basis for dynamic regulation of the human 26S proteasome | ||||||
Components |
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Keywords | HYDROLASE / ubiquitin-proteasome system / AAA-ATPase | ||||||
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 / purine ribonucleoside triphosphate binding / integrator complex / 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 / purine ribonucleoside triphosphate binding / integrator complex / meiosis I / 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 / 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 / Regulation of ornithine decarboxylase (ODC) / Homologous DNA Pairing and Strand Exchange / 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 / 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 / mRNA export from nucleus / enzyme regulator activity / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / regulation of proteasomal protein catabolic process / ERAD pathway / inclusion body / negative regulation of inflammatory response to antigenic stimulus / sarcomere / proteasome complex / ciliary basal body / Regulation of activated PAK-2p34 by proteasome mediated degradation / 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 / stem cell differentiation / SCF-beta-TrCP mediated degradation of Emi1 / Asymmetric localization of PCP proteins / 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 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / lipopolysaccharide binding / Hh mutants are degraded by ERAD / Degradation of AXIN / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / G2/M Checkpoints / P-body / Autodegradation of the E3 ubiquitin ligase COP1 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / Regulation of RUNX3 expression and activity / double-strand break repair via homologous recombination / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / MAPK6/MAPK4 signaling / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 8 Å | ||||||
Authors | Chen, S. / Wu, J. / Lu, Y. / Ma, Y.B. / Lee, B.H. / Yu, Z. / Ouyang, Q. / Finley, D. / Kirschner, M.W. / Mao, Y. | ||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2016 Title: Structural basis for dynamic regulation of the human 26S proteasome. Authors: Shuobing Chen / Jiayi Wu / Ying Lu / Yong-Bei Ma / Byung-Hoon Lee / Zhou Yu / Qi Ouyang / Daniel J Finley / Marc W Kirschner / Youdong Mao / Abstract: The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) ...The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states. The substrate-unfolding AAA-ATPase channel is narrowed by 10 inward-facing pore loops arranged into two helices that run in parallel with each other, one hydrophobic in character and the other highly charged. The gate of the core particle was unexpectedly found closed in the ground state and open in only one of the alternative states. Coordinated, stepwise conformational changes of the regulatory particle couple ATP hydrolysis to substrate translocation and regulate gating of the core particle, leading to processive degradation. | ||||||
History |
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-Structure visualization
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
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PDBx/mmCIF format | 5t0j.cif.gz | 3.7 MB | Display | PDBx/mmCIF format |
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PDB format | pdb5t0j.ent.gz | 3.2 MB | Display | PDB format |
PDBx/mmJSON format | 5t0j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5t0j_validation.pdf.gz | 776 KB | Display | wwPDB validaton report |
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Full document | 5t0j_full_validation.pdf.gz | 791.3 KB | Display | |
Data in XML | 5t0j_validation.xml.gz | 189.3 KB | Display | |
Data in CIF | 5t0j_validation.cif.gz | 320.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t0/5t0j ftp://data.pdbj.org/pub/pdb/validation_reports/t0/5t0j | HTTPS FTP |
-Related structure data
Related structure data | 8337MC 8332C 8333C 8334C 8335C 8336C 5t0cC 5t0gC 5t0hC 5t0iC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10072 (Title: Structural basis for dynamic regulation of the human 26S proteasome Data size: 2.0 TB Data #1: Drift-corrected micrographs of human 26S proteasome holoenzyme [micrographs - single frame] Data #2: Classified particle datasets for the human proteasome in four conformational states [picked particles - multiframe - processed]) |
-Links
-Assembly
Deposited unit |
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-Components
-26S proteasome non-ATPase regulatory subunit ... , 11 types, 11 molecules fUVWXYZabcd
#1: Protein | Mass: 82278.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q13200 |
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#22: Protein | Mass: 105958.234 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q99460 |
#23: Protein | Mass: 60935.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O43242 |
#24: Protein | Mass: 52979.359 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O00232 |
#25: Protein | Mass: 47526.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O00231 |
#26: Protein | Mass: 45592.285 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q15008 |
#27: Protein | Mass: 37086.441 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P51665 |
#28: Protein | Mass: 42995.359 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9UNM6 |
#29: Protein | Mass: 40781.590 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P55036 |
#30: Protein | Mass: 34488.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: O00487, Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases |
#31: Protein | Mass: 39536.676 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P48556 |
-Proteasome subunit alpha type- ... , 7 types, 7 molecules GHIJKLM
#2: Protein | Mass: 27301.262 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P60900, proteasome endopeptidase complex |
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#3: Protein | Mass: 25796.338 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25787, proteasome endopeptidase complex |
#4: Protein | Mass: 29394.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25789, proteasome endopeptidase complex |
#5: Protein | Mass: 27798.695 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: O14818, proteasome endopeptidase complex |
#6: Protein | Mass: 26304.779 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28066, proteasome endopeptidase complex |
#7: Protein | Mass: 30150.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25786, proteasome endopeptidase complex |
#8: Protein | Mass: 28338.057 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25788, proteasome endopeptidase complex |
-Proteasome subunit beta type- ... , 7 types, 7 molecules NOPQRST
#9: Protein | Mass: 25246.455 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28072, proteasome endopeptidase complex |
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#10: Protein | Mass: 29869.223 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: Q99436, proteasome endopeptidase complex |
#11: Protein | Mass: 22841.701 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P49720, proteasome endopeptidase complex |
#12: Protein | Mass: 22864.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P49721, proteasome endopeptidase complex |
#13: Protein | Mass: 28379.053 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28074, proteasome endopeptidase complex |
#14: Protein | Mass: 26391.201 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P20618, proteasome endopeptidase complex |
#15: Protein | Mass: 29099.986 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28070, proteasome endopeptidase complex |
-26S protease regulatory subunit ... , 6 types, 6 molecules ABDEFC
#16: Protein | Mass: 48700.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P35998 |
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#17: Protein | Mass: 49260.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62191 |
#18: Protein | Mass: 47426.141 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P43686 |
#19: Protein | Mass: 45867.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A0A087X2I1, UniProt: P62333*PLUS |
#20: Protein | Mass: 49266.457 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P17980 |
#21: Protein | Mass: 44852.121 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62195 |
-Protein , 1 types, 1 molecules e
#32: Protein | Mass: 8284.611 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60896 |
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-Non-polymers , 2 types, 5 molecules
#33: Chemical | ChemComp-ATP / #34: Chemical | ChemComp-ZN / | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Human 26S proteasome holoenzyme / Type: COMPLEX / Entity ID: #1-#32 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 2.5 MDa / Experimental value: YES |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 14382 / Symmetry type: POINT |