+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-14205 | |||||||||
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Title | Proteasome-ZFAND5 Complex Z+E state | |||||||||
Map data | ZFAND5-proteasome complex Z E state | |||||||||
Sample |
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Keywords | proteasome / ZFAND5 / Activation / STRUCTURAL PROTEIN | |||||||||
Function / homology | Function and homology information Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / 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 / proteasome regulatory particle / cytosolic proteasome complex ...Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / 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 / proteasome regulatory particle / cytosolic proteasome complex / positive regulation of proteasomal protein catabolic process / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / metal-dependent deubiquitinase activity / regulation of endopeptidase activity / protein K63-linked deubiquitination / 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) / Regulation of ornithine decarboxylase (ODC) / 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 / myofibril / immune system process / proteasome binding / regulation of protein catabolic process / proteasome storage granule / Presynaptic phase of homologous DNA pairing and strand exchange / blastocyst development / NF-kappaB binding / endopeptidase activator activity / polyubiquitin modification-dependent protein binding / proteasome assembly / protein deubiquitination / 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 / inclusion body / sarcomere / proteasome complex / ciliary basal body / Regulation of activated PAK-2p34 by proteasome mediated degradation / 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 / stem cell differentiation / TNFR2 non-canonical NF-kB pathway / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Degradation of DVL / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling / negative regulation of inflammatory response to antigenic stimulus / lipopolysaccharide binding / Hh mutants are degraded by ERAD / Degradation of AXIN / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / G2/M Checkpoints / Defective CFTR causes cystic fibrosis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / double-strand break repair via homologous recombination / P-body / Autodegradation of the E3 ubiquitin ligase COP1 / Vif-mediated degradation of APOBEC3G / Regulation of RUNX3 expression and activity / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / MAPK6/MAPK4 signaling / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / response to virus / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / ABC-family proteins mediated transport / HDR through Homologous Recombination (HRR) / response to organic cyclic compound / CDK-mediated phosphorylation and removal of Cdc6 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
Authors | Zhu Y / Lu Y | |||||||||
Funding support | 1 items
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Citation | Journal: Mol Cell / Year: 2023 Title: 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. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_14205.map.gz | 114.5 MB | EMDB map data format | |
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Header (meta data) | emd-14205-v30.xml emd-14205.xml | 46.9 KB 46.9 KB | Display Display | EMDB header |
Images | emd_14205.png | 116.1 KB | ||
Filedesc metadata | emd-14205.cif.gz | 13.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-14205 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14205 | HTTPS FTP |
-Validation report
Summary document | emd_14205_validation.pdf.gz | 639.8 KB | Display | EMDB validaton report |
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Full document | emd_14205_full_validation.pdf.gz | 639.3 KB | Display | |
Data in XML | emd_14205_validation.xml.gz | 6.6 KB | Display | |
Data in CIF | emd_14205_validation.cif.gz | 7.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14205 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14205 | HTTPS FTP |
-Related structure data
Related structure data | 7qxxMC 7qxnC 7qxpC 7qxuC 7qxwC 7qy7C 7qyaC 7qybC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_14205.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | ZFAND5-proteasome complex Z E state | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.37 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : human proteasome zfand5 complex Z+B state
+Supramolecule #1: human proteasome zfand5 complex Z+B state
+Macromolecule #1: 26S proteasome non-ATPase regulatory subunit 1
+Macromolecule #2: 26S proteasome non-ATPase regulatory subunit 3
+Macromolecule #3: 26S proteasome non-ATPase regulatory subunit 12
+Macromolecule #4: 26S proteasome non-ATPase regulatory subunit 11
+Macromolecule #5: 26S proteasome non-ATPase regulatory subunit 6
+Macromolecule #6: 26S proteasome non-ATPase regulatory subunit 7
+Macromolecule #7: 26S proteasome non-ATPase regulatory subunit 13
+Macromolecule #8: 26S proteasome non-ATPase regulatory subunit 4
+Macromolecule #9: 26S proteasome non-ATPase regulatory subunit 14
+Macromolecule #10: 26S proteasome non-ATPase regulatory subunit 8
+Macromolecule #11: 26S proteasome complex subunit SEM1
+Macromolecule #12: 26S proteasome non-ATPase regulatory subunit 2
+Macromolecule #13: 26S protease regulatory subunit 7
+Macromolecule #14: 26S proteasome regulatory subunit 4
+Macromolecule #15: 26S proteasome regulatory subunit 8
+Macromolecule #16: 26S protease regulatory subunit 6B
+Macromolecule #17: 26S proteasome regulatory subunit 10B
+Macromolecule #18: 26S protease regulatory subunit 6A
+Macromolecule #19: Proteasome subunit alpha type-6
+Macromolecule #20: Proteasome subunit alpha type-2
+Macromolecule #21: Proteasome subunit alpha type-4
+Macromolecule #22: Proteasome subunit alpha type-7
+Macromolecule #23: Proteasome subunit alpha type-5
+Macromolecule #24: Isoform Long of Proteasome subunit alpha type-1
+Macromolecule #25: Proteasome subunit alpha type-3
+Macromolecule #26: Proteasome subunit beta type-6
+Macromolecule #27: Proteasome subunit beta type-7
+Macromolecule #28: Proteasome subunit beta type-3
+Macromolecule #29: Proteasome subunit beta type-2
+Macromolecule #30: Proteasome subunit beta type-5
+Macromolecule #31: Proteasome subunit beta type-1
+Macromolecule #32: Proteasome subunit beta type-4
+Macromolecule #33: ZINC ION
+Macromolecule #34: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #35: MAGNESIUM ION
+Macromolecule #36: ADENOSINE-5'-DIPHOSPHATE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 46.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 28928 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |