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Open data
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Basic information
Entry | Database: PDB / ID: 8dwt | ||||||
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Title | SPOP W22R Form 2 | ||||||
![]() | Speckle-type POZ protein | ||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Cuneo, M.J. / Mittag, T. / O'Flynn, B. / Lo, Y.H. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Higher-order SPOP assembly reveals a basis for cancer mutant dysregulation. Authors: Matthew J Cuneo / Brian G O'Flynn / Yu-Hua Lo / Nafiseh Sabri / Tanja Mittag / ![]() Abstract: The speckle-type POZ protein (SPOP) functions in the Cullin3-RING ubiquitin ligase (CRL3) as a receptor for the recognition of substrates involved in cell growth, survival, and signaling. SPOP ...The speckle-type POZ protein (SPOP) functions in the Cullin3-RING ubiquitin ligase (CRL3) as a receptor for the recognition of substrates involved in cell growth, survival, and signaling. SPOP mutations have been attributed to the development of many types of cancers, including prostate and endometrial cancers. Prostate cancer mutations localize in the substrate-binding site of the substrate recognition (MATH) domain and reduce or prevent binding. However, most endometrial cancer mutations are dispersed in seemingly inconspicuous solvent-exposed regions of SPOP, offering no clear basis for their cancer-causing and peculiar gain-of-function properties. Herein, we present the first structure of SPOP in its oligomeric form, uncovering several new interfaces important for SPOP self-assembly and normal function. Given that many previously unaccounted-for cancer mutations are localized in these newly identified interfaces, we uncover molecular mechanisms underlying dysregulation of SPOP function, with effects ranging from gross structural changes to enhanced self-association, and heightened stability and activity. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 698.7 KB | Display | ![]() |
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PDB format | ![]() | 590.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27759MC ![]() 8dwsC ![]() 8dwuC ![]() 8dwvC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 42023.148 Da / Num. of mol.: 12 / Mutation: W22R Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: SPOP W22R Mutant (tetrameric form) / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7.5 / Details: 20 mM HEPES pH 7.5, 400 mM NaCl, 5 mM DTT |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % |
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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![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 69.2 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
3D reconstruction![]() | Resolution: 6.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 121000 / Symmetry type: POINT | |||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL | |||||||||||||||
Atomic model building | PDB-ID: 3HQI Accession code: 3HQI / Source name: PDB / Type: experimental model |