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- PDB-5t0g: Structural basis for dynamic regulation of the human 26S proteasome -
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Basic information
Entry | Database: PDB / ID: 5t0g | ||||||
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Title | Structural basis for dynamic regulation of the human 26S proteasome | ||||||
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![]() | HYDROLASE / ubiquitin-proteasome system / AAA-ATPase | ||||||
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 / proteasome accessory complex / integrator 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 / proteasome accessory complex / integrator 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 / proteasome regulatory particle, base subcomplex / protein K63-linked deubiquitination / metal-dependent deubiquitinase activity / regulation of endopeptidase activity / negative regulation of programmed cell death / 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 / Regulation of ornithine decarboxylase (ODC) / 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 / NF-kappaB binding / endopeptidase activator activity / polyubiquitin modification-dependent protein binding / proteasome assembly / proteasome endopeptidase complex / positive regulation of RNA polymerase II transcription preinitiation complex assembly / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / mRNA export from nucleus / enzyme regulator activity / regulation of proteasomal protein catabolic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / ERAD pathway / inclusion body / negative regulation of inflammatory response to antigenic stimulus / : / sarcomere / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / 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 / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / 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 / stem cell differentiation / CDK-mediated phosphorylation and removal of Cdc6 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Hh mutants are degraded by ERAD / lipopolysaccharide binding / SCF(Skp2)-mediated degradation of p27/p21 / Degradation of AXIN / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Hedgehog ligand biogenesis / Defective CFTR causes cystic fibrosis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / G2/M Checkpoints / Vif-mediated degradation of APOBEC3G / Autodegradation of the E3 ubiquitin ligase COP1 / Hedgehog 'on' state / Regulation of RUNX3 expression and activity / P-body / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Orc1 removal from chromatin / double-strand break repair via homologous recombination Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | ||||||
![]() | Chen, S. / Wu, J. / Lu, Y. / Ma, Y.B. / Lee, B.H. / Yu, Z. / Ouyang, Q. / Finley, D. / Kirschner, M.W. / Mao, Y. | ||||||
![]() | ![]() 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: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 3.8 MB | Display | ![]() |
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PDB format | ![]() | 3.2 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 882.2 KB | Display | ![]() |
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Full document | ![]() | 896.6 KB | Display | |
Data in XML | ![]() | 192.2 KB | Display | |
Data in CIF | ![]() | 329.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8334MC ![]() 8332C ![]() 8333C ![]() 8335C ![]() 8336C ![]() 8337C ![]() 5t0cC ![]() 5t0hC ![]() 5t0iC ![]() 5t0jC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() 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]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Proteasome subunit alpha type- ... , 7 types, 7 molecules GHIJKLM
#1: Protein | Mass: 27301.262 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P60900, proteasome endopeptidase complex |
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#2: Protein | Mass: 25796.338 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P25787, proteasome endopeptidase complex |
#3: Protein | Mass: 29394.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P25789, proteasome endopeptidase complex |
#4: Protein | Mass: 27798.695 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: O14818, proteasome endopeptidase complex |
#5: Protein | Mass: 26304.779 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P28066, proteasome endopeptidase complex |
#6: Protein | Mass: 30150.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P25786, proteasome endopeptidase complex |
#7: Protein | Mass: 28338.057 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P25788, proteasome endopeptidase complex |
-Proteasome subunit beta type- ... , 7 types, 7 molecules NOPQRST
#8: Protein | Mass: 25246.455 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P28072, proteasome endopeptidase complex |
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#9: Protein | Mass: 29869.223 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: Q99436, proteasome endopeptidase complex |
#10: Protein | Mass: 22841.701 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P49720, proteasome endopeptidase complex |
#11: Protein | Mass: 22864.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P49721, proteasome endopeptidase complex |
#12: Protein | Mass: 28379.053 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P28074, proteasome endopeptidase complex |
#13: Protein | Mass: 26391.201 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P20618, proteasome endopeptidase complex |
#14: Protein | Mass: 29099.986 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P28070, proteasome endopeptidase complex |
-26S protease regulatory subunit ... , 6 types, 6 molecules ABDEFC
#15: Protein | Mass: 48700.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#16: Protein | Mass: 49260.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#17: Protein | Mass: 47426.141 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#18: Protein | Mass: 45867.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#19: Protein | Mass: 49266.457 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#20: Protein | Mass: 44852.121 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-26S proteasome non-ATPase regulatory subunit ... , 11 types, 11 molecules UVWXYZabcdf
#21: Protein | Mass: 105958.234 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#22: Protein | Mass: 60935.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#23: Protein | Mass: 52979.359 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#24: Protein | Mass: 47526.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#25: Protein | Mass: 45592.285 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#26: Protein | Mass: 37086.441 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#27: Protein | Mass: 42995.359 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#28: Protein | Mass: 40781.590 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#29: Protein | Mass: 34488.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: O00487, Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases |
#30: Protein | Mass: 39536.676 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#32: Protein | Mass: 82278.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein , 1 types, 1 molecules e
#31: Protein | Mass: 8284.611 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-Non-polymers , 2 types, 7 molecules ![](data/chem/img/ATP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ZN.gif)
#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 |
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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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 139236 / Symmetry type: POINT |