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Open data
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Basic information
| Entry | Database: PDB / ID: 7qxp | |||||||||||||||||||||||||||
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| Title | Proteasome-ZFAND5 Complex Z+B state | |||||||||||||||||||||||||||
Components |
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Keywords | STRUCTURAL PROTEIN / proteasome / ZFAND5 / Activation | |||||||||||||||||||||||||||
| Function / homology | Function and homology informationthyrotropin-releasing hormone receptor binding / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / nuclear proteasome complex / host-mediated perturbation of viral transcription / positive regulation of inclusion body assembly / proteasome accessory complex / integrator complex / meiosis I / purine ribonucleoside triphosphate binding ...thyrotropin-releasing hormone receptor binding / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / nuclear proteasome complex / host-mediated perturbation of viral transcription / positive regulation of inclusion body assembly / proteasome accessory complex / integrator complex / meiosis I / purine ribonucleoside triphosphate binding / proteasome regulatory particle / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / sperm glycocalyx / proteasome-activating activity / Antigen processing: Ub, ATP-independent proteasomal degradation / perinuclear theca / proteasome regulatory particle, lid subcomplex / proteasome regulatory particle, base subcomplex / protein K63-linked deubiquitination / negative regulation of programmed cell death / Regulation of ornithine decarboxylase (ODC) / metal-dependent deubiquitinase activity / Proteasome assembly / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) / Somitogenesis / 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) / K63-linked deubiquitinase activity / transcription factor binding / Resolution of D-loop Structures through Holliday Junction Intermediates / sperm head-tail coupling apparatus / proteasome binding / Impaired BRCA2 binding to RAD51 / myofibril / regulation of protein catabolic process / proteasome storage granule / proteasomal ubiquitin-independent protein catabolic process / Presynaptic phase of homologous DNA pairing and strand exchange / general transcription initiation factor binding / protein deubiquitination / polyubiquitin modification-dependent protein binding / blastocyst development / immune system process / NF-kappaB binding / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / endopeptidase activator activity / threonine-type endopeptidase activity / proteasome assembly / mRNA export from nucleus / proteasome core complex, alpha-subunit complex / enzyme regulator activity / regulation of proteasomal protein catabolic process / inclusion body / ciliary tip / TBP-class protein binding / proteasome complex / : / stem cell differentiation / sarcomere / sperm end piece / Regulation of activated PAK-2p34 by proteasome mediated degradation / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / ubiquitin binding / Asymmetric localization of PCP proteins / centriole / Ubiquitin-dependent degradation of Cyclin D / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / TNFR2 non-canonical NF-kB pathway / AUF1 (hnRNP D0) binds and destabilizes mRNA / negative regulation of inflammatory response to antigenic stimulus / Assembly of the pre-replicative complex / P-body / Vpu mediated degradation of CD4 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of CRY and PER proteins / lipopolysaccharide binding / Degradation of AXIN / Hh mutants are degraded by ERAD / Activation of NF-kappaB in B cells / G2/M Checkpoints / Hedgehog ligand biogenesis / Degradation of GLI1 by the proteasome / Defective CFTR causes cystic fibrosis / Autodegradation of the E3 ubiquitin ligase COP1 / Regulation of RUNX3 expression and activity / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / Hedgehog 'on' state / 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: 3.6 Å | |||||||||||||||||||||||||||
Authors | Zhu, Y. / Lu, Y. | |||||||||||||||||||||||||||
| Funding support | 1items
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Citation | Journal: Mol Cell / Year: 2023Title: Molecular mechanism for activation of the 26S proteasome by ZFAND5. Authors: Donghoon Lee / Yanan Zhu / Louis Colson / Xiaorong Wang / Siyi Chen / Emre Tkacik / Lan Huang / Qi Ouyang / Alfred L Goldberg / Ying Lu / ![]() Abstract: Various hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated proteins can increase, we studied mouse ...Various hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated proteins can increase, we studied mouse ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5's AN1 Zn-finger domain interacts with the Rpt5 ATPase and its C terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Upon proteasome binding, ZFAND5 widens the entrance of the substrate translocation channel, yet it associates only transiently with the proteasome. Dissociation of ZFAND5 then stimulates opening of the 20S proteasome gate. Using single-molecule microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis. | |||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 7qxp.cif.gz | 2.3 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb7qxp.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 7qxp.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qx/7qxp ftp://data.pdbj.org/pub/pdb/validation_reports/qx/7qxp | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 14202MC ![]() 7qxnC ![]() 7qxuC ![]() 7qxwC ![]() 7qxxC ![]() 7qy7C ![]() 7qyaC ![]() 7qybC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-26S proteasome ... , 13 types, 13 molecules UVWXYZabcdefE
| #1: Protein | Mass: 105958.234 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD1 / Production host: Homo sapiens (human) / References: UniProt: Q99460 |
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| #2: Protein | Mass: 60935.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD3 / Production host: Homo sapiens (human) / References: UniProt: O43242 |
| #3: Protein | Mass: 52979.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD12 / Production host: Homo sapiens (human) / References: UniProt: O00232 |
| #4: Protein | Mass: 47526.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD11 / Production host: Homo sapiens (human) / References: UniProt: O00231 |
| #5: Protein | Mass: 45592.285 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD6, KIAA0107, PFAAP4 / Production host: Homo sapiens (human) / References: UniProt: Q15008 |
| #6: Protein | Mass: 37086.441 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD7, MOV34L / Production host: Homo sapiens (human) / References: UniProt: P51665 |
| #7: Protein | Mass: 42995.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD13 / Production host: Homo sapiens (human) / References: UniProt: Q9UNM6 |
| #8: Protein | Mass: 40781.590 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD4, MCB1 / Production host: Homo sapiens (human) / References: UniProt: P55036 |
| #9: Protein | Mass: 34488.824 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD14, POH1 / Production host: 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 genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD8 / Production host: Homo sapiens (human) / References: UniProt: P48556 |
| #11: Protein | Mass: 8284.611 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SEM1, C7orf76, DSS1, SHFDG1, SHFM1 / Production host: Homo sapiens (human) / References: UniProt: P60896 |
| #12: Protein | Mass: 100313.625 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMD2, TRAP2 / Production host: Homo sapiens (human) / References: UniProt: Q13200 |
| #17: Protein | Mass: 45867.027 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMC6 / Production host: Homo sapiens (human) / References: UniProt: A0A087X2I1 |
-26S protease regulatory subunit ... , 4 types, 4 molecules ABDF
| #13: Protein | Mass: 48700.805 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMC2, MSS1 / Production host: 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 genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMC1 / Production host: Homo sapiens (human) / References: UniProt: P62191 |
| #16: Protein | Mass: 47426.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMC4, MIP224, TBP7 / Production host: Homo sapiens (human) / References: UniProt: P43686 |
| #18: Protein | Mass: 49266.457 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMC3, TBP1 / Production host: Homo sapiens (human) / References: UniProt: P17980 |
-Protein , 2 types, 3 molecules CLl
| #15: Protein | Mass: 44852.121 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMC5, SUG1 / Production host: Homo sapiens (human) / References: UniProt: P62195 |
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| #24: Protein | Mass: 30150.277 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA1, HC2, NU, PROS30, PSC2 / Production host: Homo sapiens (human) / References: UniProt: P25786 |
-Proteasome subunit alpha type- ... , 6 types, 12 molecules GgHhIiJjKkMm
| #19: Protein | Mass: 27301.262 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA6, PROS27 / Production host: Homo sapiens (human) / References: UniProt: P60900#20: Protein | Mass: 25796.338 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA2, HC3, PSC3 / Production host: Homo sapiens (human) / References: UniProt: P25787#21: Protein | Mass: 29394.648 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA4, HC9, PSC9 / Production host: Homo sapiens (human) / References: UniProt: P25789#22: Protein | Mass: 27798.695 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA7, HSPC / Production host: Homo sapiens (human) / References: UniProt: O14818#23: Protein | Mass: 26304.779 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA5 / Production host: Homo sapiens (human) / References: UniProt: P28066#25: Protein | Mass: 28338.057 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMA3, HC8, PSC8 / Production host: Homo sapiens (human) / References: UniProt: P25788 |
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-Proteasome subunit beta type- ... , 7 types, 14 molecules NnOoPpQqRrSsTt
| #26: Protein | Mass: 25246.455 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB6, LMPY, Y / Production host: Homo sapiens (human)References: UniProt: P28072, proteasome endopeptidase complex #27: Protein | Mass: 29869.223 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB7, Z / Production host: Homo sapiens (human)References: UniProt: Q99436, proteasome endopeptidase complex #28: Protein | Mass: 22841.701 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB3 / Production host: Homo sapiens (human)References: UniProt: P49720, proteasome endopeptidase complex #29: Protein | Mass: 22864.277 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB2 / Production host: Homo sapiens (human)References: UniProt: P49721, proteasome endopeptidase complex #30: Protein | Mass: 28379.053 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB5, LMPX, MB1, X / Production host: Homo sapiens (human)References: UniProt: P28074, proteasome endopeptidase complex #31: Protein | Mass: 26391.201 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB1, PSC5 / Production host: Homo sapiens (human) / References: UniProt: P20618#32: Protein | Mass: 29099.986 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSMB4, PROS26 / Production host: Homo sapiens (human) / References: UniProt: P28070 |
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-Non-polymers , 4 types, 12 molecules 






| #33: Chemical | ChemComp-ZN / | ||||
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| #34: Chemical | ChemComp-ATP / #35: Chemical | ChemComp-MG / #36: Chemical | |
-Details
| Has ligand of interest | Y |
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| Has protein modification | N |
-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 proteasome zfand5 complex Z+B state / Type: COMPLEX / Entity ID: #1-#32 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7 |
| Specimen | Conc.: 2 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: 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 / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm |
| Image recording | Electron dose: 46.6 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
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Processing
| Software | Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement | ||||||||||||||||||||||||
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| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 90097 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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Homo sapiens (human)
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