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Yorodumi- PDB-6wjd: SA-like state of human 26S Proteasome with non-cleavable M1-linke... -
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-Basic information
Entry | Database: PDB / ID: 6wjd | ||||||||||||
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Title | SA-like state of human 26S Proteasome with non-cleavable M1-linked hexaubiquitin and E3 ubiquitin ligase E6AP/UBE3A | ||||||||||||
Components |
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Keywords | HYDROLASE/PROTEIN BINDING / 26S protease / ubiquitin / complex / subunit / HYDROLASE-PROTEIN BINDING complex | ||||||||||||
Function / homology | Function and homology information Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / meiosis I / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex / proteasome regulatory particle ...Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / thyrotropin-releasing hormone receptor binding / modulation by host of viral transcription / meiosis I / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / proteasome accessory complex / purine ribonucleoside triphosphate binding / integrator complex / 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 / Regulation of ornithine decarboxylase (ODC) / 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) / proteasome core complex / Resolution of D-loop Structures through Holliday Junction Intermediates / Cross-presentation of soluble exogenous antigens (endosomes) / K63-linked deubiquitinase activity / Somitogenesis / : / Impaired BRCA2 binding to RAD51 / immune system process / myofibril / proteasome binding / regulation of protein catabolic process / transcription factor binding / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / blastocyst development / general transcription initiation factor binding / polyubiquitin modification-dependent protein binding / NF-kappaB binding / endopeptidase activator activity / proteasome 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 / regulation of proteasomal protein catabolic process / negative regulation of inflammatory response to antigenic stimulus / inclusion body / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / FLT3 signaling by CBL mutants / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Glycogen synthesis / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / TICAM1,TRAF6-dependent induction of TAK1 complex / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of FZD by ubiquitination / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / p75NTR recruits signalling complexes / APC/C:Cdc20 mediated degradation of Cyclin B / VLDLR internalisation and degradation / Downregulation of ERBB4 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / sarcomere / Regulation of innate immune responses to cytosolic DNA / NF-kB is activated and signals survival / InlA-mediated entry of Listeria monocytogenes into host cells / Regulation of pyruvate metabolism / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Pexophagy / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of PTEN localization / proteasome complex / Regulation of BACH1 activity / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / TICAM1, RIP1-mediated IKK complex recruitment / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.8 Å | ||||||||||||
Authors | Chen, X. / Walters, K.J. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: Structure / Year: 2020 Title: Cryo-EM Reveals Unanchored M1-Ubiquitin Chain Binding at hRpn11 of the 26S Proteasome. Authors: Xiang Chen / Zachary Dorris / Dan Shi / Rick K Huang / Htet Khant / Tara Fox / Natalia de Val / Dewight Williams / Ping Zhang / Kylie J Walters / Abstract: The 26S proteasome is specialized for regulated protein degradation and formed by a dynamic regulatory particle (RP) that caps a hollow cylindrical core particle (CP) where substrates are proteolyzed. ...The 26S proteasome is specialized for regulated protein degradation and formed by a dynamic regulatory particle (RP) that caps a hollow cylindrical core particle (CP) where substrates are proteolyzed. Its diverse substrates unify as proteasome targets by ubiquitination. We used cryogenic electron microscopy (cryo-EM) to study how human 26S proteasome interacts with M1-linked hexaubiquitin (M1-Ub) unanchored to a substrate and E3 ubiquitin ligase E6AP/UBE3A. Proteasome structures are available with model substrates extending through the RP ATPase ring and substrate-conjugated K63-linked ubiquitin chains present at inhibited deubiquitinating enzyme hRpn11 and the nearby ATPase hRpt4/hRpt5 coiled coil. In this study, we find M1-Ub at the hRpn11 site despite the absence of conjugated substrate, indicating that ubiquitin binding at this location does not require substrate interaction with the RP. Moreover, unanchored M1-Ub binds to this hRpn11 site of the proteasome with the CP gating residues in both the closed and opened conformational states. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6wjd.cif.gz | 2.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6wjd.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6wjd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wjd_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6wjd_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 6wjd_validation.xml.gz | 295.8 KB | Display | |
Data in CIF | 6wjd_validation.cif.gz | 478.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wj/6wjd ftp://data.pdbj.org/pub/pdb/validation_reports/wj/6wjd | HTTPS FTP |
-Related structure data
Related structure data | 21691MC 6wjnC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10401 (Title: SA-like and SD-like states of human 26S Proteasome with non-cleavable M1-linked hexaubiquitin and E3 ubiquitin ligase E6AP/UBE3A Data size: 330.3 Data #1: Motion-corrected single frame micrographs of human 26S Proteasome with non-cleavable M1-linked hexaubiquitin and E3 ubiquitin ligase E6AP/UBE3A [micrographs - single frame]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-26S proteasome non-ATPase regulatory subunit ... , 11 types, 11 molecules UVWXYZabcdf
#1: Protein | Mass: 105958.234 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q99460 |
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#2: Protein | Mass: 61066.500 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O43242 |
#3: Protein | Mass: 52979.359 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O00232 |
#4: Protein | Mass: 47526.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O00231 |
#5: Protein | Mass: 45592.285 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q15008 |
#6: Protein | Mass: 37086.441 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P51665 |
#7: Protein | Mass: 42995.359 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9UNM6 |
#8: Protein | Mass: 40781.590 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P55036 |
#9: 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 |
#10: Protein | Mass: 39536.676 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P48556 |
#12: Protein | Mass: 100313.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q13200 |
-Protein , 2 types, 2 molecules eu
#11: 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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#19: Protein | Mass: 8576.831 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P0CG48 |
-26S proteasome regulatory subunit ... , 6 types, 6 molecules ABCDEF
#13: 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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#14: Protein | Mass: 49260.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62191 |
#15: Protein | Mass: 44852.121 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62195 |
#16: Protein | Mass: 47426.141 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P43686 |
#17: Protein | Mass: 45867.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A0A087X2I1 |
#18: Protein | Mass: 49266.457 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P17980 |
-Proteasome subunit alpha type- ... , 7 types, 14 molecules GgHhIiJjKkLlMm
#20: Protein | Mass: 27301.262 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P60900, proteasome endopeptidase complex #21: Protein | Mass: 25796.338 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25787, proteasome endopeptidase complex #22: Protein | Mass: 29394.648 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25789, proteasome endopeptidase complex #23: Protein | Mass: 27798.695 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: O14818, proteasome endopeptidase complex #24: Protein | Mass: 26304.779 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28066, proteasome endopeptidase complex #25: Protein | Mass: 30150.277 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25786, proteasome endopeptidase complex #26: Protein | Mass: 28338.057 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P25788, proteasome endopeptidase complex |
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-Proteasome subunit beta type- ... , 7 types, 14 molecules NnOoPpQqRrSsTt
#27: Protein | Mass: 25246.455 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28072, proteasome endopeptidase complex #28: Protein | Mass: 29869.223 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: Q99436, proteasome endopeptidase complex #29: Protein | Mass: 22841.701 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P49720, proteasome endopeptidase complex #30: Protein | Mass: 22864.277 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P49721, proteasome endopeptidase complex #31: Protein | Mass: 28379.053 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28074, proteasome endopeptidase complex #32: Protein | Mass: 26391.201 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P20618, proteasome endopeptidase complex #33: Protein | Mass: 29099.986 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P28070, proteasome endopeptidase complex |
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-Non-polymers , 4 types, 12 molecules
#34: Chemical | ChemComp-ZN / | ||||
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#35: Chemical | ChemComp-AGS / #36: Chemical | ChemComp-MG / #37: Chemical | |
-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 |
-Sample preparation
Component | Name: Human 26S Proteasome with non-cleavable M1-linked hexaubiquitin and E3 ubiquitin ligase E6AP/UBE3A Type: COMPLEX / Entity ID: #1-#33 / Source: NATURAL | |||||||||||||||||||||||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 Details: 50 mM Tris, pH 7.5, 50 mM NaCl, 1.5 mM ATP-gamma-S, 5 mM MgCl2, 2 mM DTT, 10 uM zinc sulfate | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 291.15 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 0.2 sec. / Electron dose: 36.64 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 6216 |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1050369 | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 37698 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6MSD Accession code: 6MSD / Source name: PDB / Type: experimental model |