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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | SPOP 12mer Double Donut | |||||||||
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Sample |
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Keywords | ubiquitination / protein degradation / protein oligomer / substrate adapter / PROTEIN BINDING | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 10.7 Å | |||||||||
Authors | Cuneo MJ | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2025Title: The equilibrium between two quaternary assembly states determines the activity of SPOP and its cancer mutants. Authors: Matthew J Cuneo / Ömer Güllülü / Mohamed-Raafet Ammar / Xinrui Gui / Kelly Churion / Martin Turk / Brian G O'Flynn / Nafiseh Sabri / Tanja Mittag / ![]() Abstract: Proteostasis is critical for preventing oncogenesis. Both activating and inactivating mutations in the ubiquitin ligase subunit SPOP result in oncogenesis in different tissues. SPOP assembles into ...Proteostasis is critical for preventing oncogenesis. Both activating and inactivating mutations in the ubiquitin ligase subunit SPOP result in oncogenesis in different tissues. SPOP assembles into filaments that are multivalent for substrates, and substrates have multiple weak motifs for SPOP that are not activated via post-translational modifications. It is thus unclear how regulation is achieved. Here, we show that SPOP filaments circularize into rings that dimerize into up to 2.5 MDa-large, auto-inhibited double donuts. The equilibrium between double donuts and linear filaments determines SPOP activity. Activating and deactivating cancer mutations shift the equilibrium towards the filament or the double donut, respectively, and this influences substrate turnover and subcellular localization. This regulatory mechanism requires long filaments that can circularize into rings, likely explaining the presence of multiple weak SPOP-binding motifs in substrates. Activating and deactivating mutations combine to give rise to intermediate activities, suggesting new levers for cancer therapies. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_71281.map.gz | 249.5 MB | EMDB map data format | |
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| Header (meta data) | emd-71281-v30.xml emd-71281.xml | 11.9 KB 11.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_71281_fsc.xml | 17.2 KB | Display | FSC data file |
| Images | emd_71281.png | 44.7 KB | ||
| Masks | emd_71281_msk_1.map | 512 MB | Mask map | |
| Filedesc metadata | emd-71281.cif.gz | 3.9 KB | ||
| Others | emd_71281_half_map_1.map.gz emd_71281_half_map_2.map.gz | 475.5 MB 475.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-71281 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-71281 | HTTPS FTP |
-Validation report
| Summary document | emd_71281_validation.pdf.gz | 982.6 KB | Display | EMDB validaton report |
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| Full document | emd_71281_full_validation.pdf.gz | 982.1 KB | Display | |
| Data in XML | emd_71281_validation.xml.gz | 26.1 KB | Display | |
| Data in CIF | emd_71281_validation.cif.gz | 34.6 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-71281 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-71281 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_71281.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.2928 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Mask #1
| File | emd_71281_msk_1.map | ||||||||||||
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-Half map: #1
| File | emd_71281_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #2
| File | emd_71281_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : SPOP 12mer double donut
| Entire | Name: SPOP 12mer double donut |
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| Components |
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-Supramolecule #1: SPOP 12mer double donut
| Supramolecule | Name: SPOP 12mer double donut / type: complex / ID: 1 / Parent: 0 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TALOS ARCTICA |
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| Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 1.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.0 µm |
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
United States, 1 items
Citation







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Y (Row.)
X (Col.)












































Processing
FIELD EMISSION GUN

