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Open data
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Basic information
Entry | Database: PDB / ID: 7qo6 | ||||||||||||||||||
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Title | 26S proteasome Rpt1-RK -Ubp6-UbVS complex in the s2 state | ||||||||||||||||||
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![]() | MOTOR PROTEIN / proteasome / ubiquitin / Ubp6 / allostery / deubiquitination | ||||||||||||||||||
Function / homology | ![]() SAGA complex localization to transcription regulatory region / transcription export complex 2 / proteasome regulatory particle assembly / maintenance of DNA trinucleotide repeats / filamentous growth / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / protein deubiquitination / proteasome core complex ...SAGA complex localization to transcription regulatory region / transcription export complex 2 / proteasome regulatory particle assembly / maintenance of DNA trinucleotide repeats / filamentous growth / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / protein deubiquitination / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) / TNFR2 non-canonical NF-kB pathway / proteasomal ubiquitin-independent protein catabolic process / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Regulation of PTEN stability and activity / KEAP1-NFE2L2 pathway / CDK-mediated phosphorylation and removal of Cdc6 / Neddylation / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / regulation of protein catabolic process / Orc1 removal from chromatin / MAPK6/MAPK4 signaling / proteasome storage granule / Antigen processing: Ubiquitination & Proteasome degradation / proteasome assembly / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / Ub-specific processing proteases / threonine-type endopeptidase activity / mRNA export from nucleus / enzyme regulator activity / protein folding chaperone / Neutrophil degranulation / proteasome complex / double-strand break repair via homologous recombination / metallopeptidase activity / protein-macromolecule adaptor activity / endopeptidase activity / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / molecular adaptor activity / regulation of cell cycle / ubiquitin protein ligase binding / structural molecule activity / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / ATP hydrolysis activity / ATP binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.3 Å | ||||||||||||||||||
![]() | Hung, K.Y.S. / Klumpe, S. / Eisele, M.R. / Elsasser, S. / Geng, T.T. / Cheng, T.C. / Joshi, T. / Rudack, T. / Sakata, E. / Finley, D. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Allosteric control of Ubp6 and the proteasome via a bidirectional switch. Authors: Ka Ying Sharon Hung / Sven Klumpe / Markus R Eisele / Suzanne Elsasser / Geng Tian / Shuangwu Sun / Jamie A Moroco / Tat Cheung Cheng / Tapan Joshi / Timo Seibel / Duco Van Dalen / Xin-Hua ...Authors: Ka Ying Sharon Hung / Sven Klumpe / Markus R Eisele / Suzanne Elsasser / Geng Tian / Shuangwu Sun / Jamie A Moroco / Tat Cheung Cheng / Tapan Joshi / Timo Seibel / Duco Van Dalen / Xin-Hua Feng / Ying Lu / Huib Ovaa / John R Engen / Byung-Hoon Lee / Till Rudack / Eri Sakata / Daniel Finley / ![]() ![]() ![]() ![]() ![]() Abstract: The proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by ...The proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by deubiquitinating enzyme Ubp6. The proteasome activates Ubp6, whereas Ubp6 inhibits the proteasome through deubiquitination and a noncatalytic effect. Here, we report cryo-EM structures of the proteasome bound to Ubp6, based on which we identify mutants in Ubp6 and proteasome subunit Rpt1 that abrogate Ubp6 activation. The Ubp6 mutations define a conserved region that we term the ILR element. The ILR is found within the BL1 loop, which obstructs the catalytic groove in free Ubp6. Rpt1-ILR interaction opens the groove by rearranging not only BL1 but also a previously undescribed network of three interconnected active-site-blocking loops. Ubp6 activation and noncatalytic proteasome inhibition are linked in that they are eliminated by the same mutations. Ubp6 and ubiquitin together drive proteasomes into a unique conformation associated with proteasome inhibition. Thus, a multicomponent allosteric switch exerts simultaneous control over both Ubp6 and the proteasome. | ||||||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 2.4 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 14085MC ![]() 7qo3C ![]() 7qo5C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 13 types, 22 molecules aAbBcCdDeEfFgGk4m6TX89
#1: Protein | Mass: 28033.830 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #2: Protein | Mass: 27191.828 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #3: Protein | Mass: 28748.230 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #4: Protein | Mass: 28478.111 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #5: Protein | Mass: 28649.086 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #6: Protein | Mass: 25634.000 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #7: Protein | Mass: 31575.068 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #11: Protein | Mass: 22545.676 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: A0A6A5Q0W2, proteasome endopeptidase complex #13: Protein | Mass: 26905.076 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #17: Protein | | Mass: 31952.119 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #18: Protein | | Mass: 17919.002 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #34: Protein | | Mass: 57188.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: PACBIOSEQ_LOCUS2079, PACBIOSEQ_LOCUS2095, PACBIOSEQ_LOCUS2109, PACBIOSEQ_LOCUS2117, PACBIOSEQ_LOCUS2154, SCNYR20_0015006200, SCP684_0015006000 Production host: ![]() ![]() #35: Protein | | Mass: 8560.831 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Proteasome subunit beta type- ... , 3 types, 6 molecules h1l5n7
#8: Protein | Mass: 23573.604 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P38624, proteasome endopeptidase complex #12: Protein | Mass: 31670.539 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: A0A6A5Q5W3, proteasome endopeptidase complex #14: Protein | Mass: 29471.289 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-Proteasome endopeptidase ... , 2 types, 4 molecules i2j3
#9: Protein | Mass: 28299.889 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: A0A6A5Q449, proteasome endopeptidase complex #10: Protein | Mass: 22627.842 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: A0A6L0YA22, proteasome endopeptidase complex |
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-26S proteasome ... , 17 types, 17 molecules WVYZNSPQRUOHIKLMJ
#15: Protein | Mass: 29776.098 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#16: Protein | Mass: 34442.281 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#19: Protein | Mass: 10397.102 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#20: Protein | Mass: 109601.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: Protein | Mass: 104351.883 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#22: Protein | Mass: 60464.605 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#23: Protein | Mass: 51840.352 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#24: Protein | Mass: 49839.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#25: Protein | Mass: 49016.367 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#26: Protein | Mass: 38365.508 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#27: Protein | Mass: 45839.348 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#28: Protein | Mass: 52153.082 Da / Num. of mol.: 1 / Mutation: S164R; T166K / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#29: Protein | Mass: 48898.160 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#30: Protein | Mass: 47953.676 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#31: Protein | Mass: 49480.137 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#32: Protein | Mass: 48315.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#33: Protein | Mass: 45342.742 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Non-polymers , 3 types, 12 molecules ![](data/chem/img/ATP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ADP.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ADP.gif)
#36: Chemical | ChemComp-ATP / #37: Chemical | ChemComp-MG / #38: Chemical | ChemComp-ADP / | |
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-Details
Has ligand of interest | N |
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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: 26S proteasome Rpt1-RK -Ubp6-UbVS complex in the s2 state Type: COMPLEX / Entity ID: #1-#35 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 2.5 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid type: Quantifoil R2/1 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1800 nm |
Image recording | Electron dose: 35 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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3D reconstruction | Resolution: 6.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 74842 / Symmetry type: POINT |