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Open data
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Basic information
Entry | Database: PDB / ID: 7qo5 | ||||||||||||||||||
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Title | 26S proteasome Rpt1-RK -Ubp6-UbVS complex in the si state | ||||||||||||||||||
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![]() | MOTOR PROTEIN / Proteasome UBP6 Ubiquitin Allostery | ||||||||||||||||||
Function / homology | ![]() SAGA complex localization to transcription regulatory region / mitochondria-associated ubiquitin-dependent protein catabolic process / Metalloprotease DUBs / peroxisome fission / negative regulation of proteasomal protein catabolic process / regulation of proteasomal ubiquitin-dependent protein catabolic process / proteasome storage granule assembly / transcription export complex 2 / proteasome regulatory particle assembly / protein deneddylation ...SAGA complex localization to transcription regulatory region / mitochondria-associated ubiquitin-dependent protein catabolic process / Metalloprotease DUBs / peroxisome fission / negative regulation of proteasomal protein catabolic process / regulation of proteasomal ubiquitin-dependent protein catabolic process / proteasome storage granule assembly / transcription export complex 2 / proteasome regulatory particle assembly / protein deneddylation / maintenance of DNA trinucleotide repeats / filamentous growth / COP9 signalosome / proteasome regulatory particle / cytosolic proteasome complex / proteasome regulatory particle, lid subcomplex / protein-containing complex localization / proteasome-activating activity / mitochondrial fission / proteasome regulatory particle, base subcomplex / metal-dependent deubiquitinase activity / hypothalamus gonadotrophin-releasing hormone neuron development / female meiosis I / positive regulation of protein monoubiquitination / nonfunctional rRNA decay / mitochondrion transport along microtubule / fat pad development / K48-linked polyubiquitin modification-dependent protein binding / proteasome core complex assembly / nuclear outer membrane-endoplasmic reticulum membrane network / 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 / peptide catabolic process / proteasome binding / CDK-mediated phosphorylation and removal of Cdc6 / Neddylation / female gonad development / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / seminiferous tubule development / regulation of protein catabolic process / Orc1 removal from chromatin / male meiosis I / MAPK6/MAPK4 signaling / proteasome storage granule / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Antigen processing: Ubiquitination & Proteasome degradation / 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 / Ub-specific processing proteases / threonine-type endopeptidase activity / mRNA export from nucleus / enzyme regulator activity / positive regulation of transcription elongation by RNA polymerase II / neuron projection morphogenesis / regulation of neuron apoptotic process / regulation of proteasomal protein catabolic process / ERAD pathway / energy homeostasis / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / protein folding chaperone / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Neutrophil degranulation / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / 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 / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / NOTCH3 Activation and Transmission of Signal to the Nucleus / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6 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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Downloads & links
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Download
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 | ![]() 14084MC ![]() 7qo3C ![]() 7qo6C 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
-Proteasome subunit alpha type- ... , 6 types, 12 molecules aAbBcCdDeEfF
#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) ![]() ![]() |
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-Protein , 2 types, 3 molecules gG9
#7: Protein | Mass: 31575.068 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #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- ... , 7 types, 14 molecules h1i2j3k4l5m6n7
#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 #9: Protein | Mass: 28299.889 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P25043, proteasome endopeptidase complex #10: Protein | Mass: 22627.842 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) ![]() ![]() #12: Protein | Mass: 31670.539 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P30656, proteasome endopeptidase complex #13: Protein | Mass: 26905.076 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #14: Protein | Mass: 29471.289 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-26S proteasome ... , 18 types, 18 molecules WTXYZNSPQRUOHIKLMJ
#15: Protein | Mass: 29776.098 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#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) ![]() ![]() |
#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) ![]() ![]() |
-Ubiquitin carboxyl-terminal hydrolase ... , 2 types, 2 molecules V8
#16: Protein | Mass: 34442.281 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#34: Protein | Mass: 57188.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Strain: ATCC 204508 / S288c / Gene: UBP6, YFR010W / Production host: ![]() ![]() |
-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
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Source (natural) |
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Source (recombinant) | 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 | ||||||||||||||||||||||||
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 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 64766 / Symmetry type: POINT |