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Open data
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Basic information
Entry | Database: PDB / ID: 8vvy | ||||||
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Title | Human Cullin-1 in complex with CAND2 | ||||||
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![]() | LIGASE / Complex | ||||||
Function / homology | ![]() SCF complex assembly / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cullin-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / SCF ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / Prolactin receptor signaling / protein monoubiquitination / protein K48-linked ubiquitination ...SCF complex assembly / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cullin-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / SCF ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / Prolactin receptor signaling / protein monoubiquitination / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / intrinsic apoptotic signaling pathway / NIK-->noncanonical NF-kB signaling / SCF-beta-TrCP mediated degradation of Emi1 / TBP-class protein binding / Dectin-1 mediated noncanonical NF-kB signaling / animal organ morphogenesis / Activation of NF-kappaB in B cells / Iron uptake and transport / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / 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 / Degradation of beta-catenin by the destruction complex / NOTCH1 Intracellular Domain Regulates Transcription / G1/S transition of mitotic cell cycle / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / Cyclin D associated events in G1 / Regulation of RUNX2 expression and activity / : / Regulation of PLK1 Activity at G2/M Transition / Downstream TCR signaling / Antigen processing: Ubiquitination & Proteasome degradation / Neddylation / protein-macromolecule adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / cell population proliferation / positive regulation of canonical NF-kappaB signal transduction / protein ubiquitination / ubiquitin protein ligase binding / positive regulation of DNA-templated transcription / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.49 Å | ||||||
![]() | Kenny, S. / Liu, X. / Das, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular mechanisms of CAND2 in regulating SCF ubiquitin ligases. Authors: Kankan Wang / Lihong Li / Sebastian Kenny / Dailin Gan / Justin M Reitsma / Yun Zhou / Chittaranjan Das / Xing Liu / ![]() Abstract: Protein degradation orchestrated by SKP1·CUL1·F-box protein (SCF) ubiquitin ligases is a fundamental process essential for cellular and organismal function. The dynamic assembly of SCFs, ...Protein degradation orchestrated by SKP1·CUL1·F-box protein (SCF) ubiquitin ligases is a fundamental process essential for cellular and organismal function. The dynamic assembly of SCFs, facilitated by CAND1, ensures timely ubiquitination of diverse SCF target proteins. As a homolog of CAND1, CAND2 alone has been implicated in various human diseases, yet its functional mechanisms remain elusive. Here, we investigate the role of CAND2 in human cells and its distinct mode of action compared to CAND1. Using an array of quantitative assays, we demonstrate that CAND2 promotes SCF-mediated protein degradation as an F-box protein exchange factor. While CAND2 binds CUL1 with structure and affinity comparable to CAND1, it exhibits lower efficiency in exchanging F-box proteins. Kinetic measurements reveal a significantly higher K for CAND2-catalyzed SCF disassembly than CAND1, which explains the lower exchange efficiency of CAND2 and is likely due to conformations of the CAND2·SCF exchange intermediate complex being less favorable for F-box protein dissociation. Our study provides mechanistic insights into the biochemical and structural properties of CAND2, as well as its role in regulating cellular dynamics of SCFs, laying a foundation for understanding contributions of CAND2 to healthy and diseased human cells. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 337.6 KB | Display | ![]() |
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PDB format | ![]() | 269.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 57.6 KB | Display | |
Data in CIF | ![]() | 86.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 43572MC 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: 86294.484 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 136669.500 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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: CAND2-CUL1 / 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: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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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 / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 4.56 sec. / Electron dose: 1.28 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5333 |
EM imaging optics | Energyfilter name: TFS Selectris X / Energyfilter slit width: 10 eV |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4562541 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.49 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 187280 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL / Target criteria: Cross-Correlation Coefficient | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Source name: AlphaFold / Type: in silico model | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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