+Open data
-Basic information
Entry | Database: PDB / ID: 7zbz | |||||||||
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Title | CAND1 delhairpin-SCF-SKP2 CAND1 partly engaged SCF partly rocked | |||||||||
Components |
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Keywords | LIGASE / cullin-RING E3 ubiquitin ligase / SCF / CAND1 / Assembly factor | |||||||||
Function / homology | Function and homology information SCF complex assembly / positive regulation of protein polyubiquitination / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / Aberrant regulation of mitotic exit in cancer due to RB1 defects / PcG protein complex / negative regulation of catalytic activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity ...SCF complex assembly / positive regulation of protein polyubiquitination / Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / Aberrant regulation of mitotic exit in cancer due to RB1 defects / PcG protein complex / negative regulation of catalytic activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / positive regulation of intracellular estrogen receptor signaling pathway / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / protein K63-linked ubiquitination / ubiquitin-like ligase-substrate adaptor activity / positive regulation of double-strand break repair via homologous recombination / positive regulation of RNA polymerase II transcription preinitiation complex assembly / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / ubiquitin ligase complex / TBP-class protein binding / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / MAP3K8 (TPL2)-dependent MAPK1/3 activation / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / molecular function activator activity / Vpu mediated degradation of CD4 / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / animal organ morphogenesis / Negative regulation of NOTCH4 signaling / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / 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 / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Degradation of beta-catenin by the destruction complex / NOTCH1 Intracellular Domain Regulates Transcription / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / beta-catenin binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / G1/S transition of mitotic cell cycle / protein polyubiquitination / G2/M transition of mitotic cell cycle / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / Regulation of PLK1 Activity at G2/M Transition / ubiquitin protein ligase activity / Circadian Clock / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Downstream TCR signaling / protein-macromolecule adaptor activity / Neddylation / mitotic cell cycle / ubiquitin-dependent protein catabolic process / regulation of apoptotic process / proteasome-mediated ubiquitin-dependent protein catabolic process / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / ficolin-1-rich granule lumen / cell population proliferation / cell differentiation / Ub-specific processing proteases / regulation of cell cycle / protein ubiquitination / chromatin remodeling / protein domain specific binding / innate immune response / centrosome / ubiquitin protein ligase binding / Neutrophil degranulation / nucleolus / Golgi apparatus / zinc ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Baek, K. / Schulman, B.A. | |||||||||
Funding support | Germany, European Union, 2items
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Citation | Journal: Cell / Year: 2023 Title: Systemwide disassembly and assembly of SCF ubiquitin ligase complexes. Authors: Kheewoong Baek / Daniel C Scott / Lukas T Henneberg / Moeko T King / Matthias Mann / Brenda A Schulman / Abstract: Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much ...Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much protein degradation, require CAND1 to distribute the limiting CUL1 subunit across the family of ∼70 different F box proteins. Yet, how a single factor coordinately assembles numerous distinct multiprotein complexes remains unknown. We obtained cryo-EM structures of CAND1-bound SCF complexes in multiple states and correlated mutational effects on structures, biochemistry, and cellular assays. The data suggest that CAND1 clasps idling catalytic domains of an inactive SCF, rolls around, and allosterically rocks and destabilizes the SCF. New SCF production proceeds in reverse, through SKP1-F box allosterically destabilizing CAND1. The CAND1-SCF conformational ensemble recycles CUL1 from inactive complexes, fueling mixing and matching of SCF parts for E3 activation in response to substrate availability. Our data reveal biogenesis of a predominant family of E3 ligases, and the molecular basis for systemwide multiprotein complex assembly. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7zbz.cif.gz | 419.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7zbz.ent.gz | 328.7 KB | Display | PDB format |
PDBx/mmJSON format | 7zbz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7zbz_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7zbz_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7zbz_validation.xml.gz | 71.3 KB | Display | |
Data in CIF | 7zbz_validation.cif.gz | 108.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zb/7zbz ftp://data.pdbj.org/pub/pdb/validation_reports/zb/7zbz | HTTPS FTP |
-Related structure data
Related structure data | 14597MC 7z8rC 7z8tC 7z8vC 7zbwC 8cdjC 8cdkC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 3 types, 3 molecules CDR
#1: Protein | Mass: 89800.367 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q13616 |
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#2: Protein | Mass: 137314.156 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CAND1, KIAA0829, TIP120, TIP120A / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q86VP6 |
#3: Protein | Mass: 12089.677 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: I2CVJ6 |
-S-phase kinase-associated protein ... , 2 types, 2 molecules SF
#4: Protein | Mass: 18679.965 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SKP1, EMC19, OCP2, SKP1A, TCEB1L / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P63208 |
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#5: Protein | Mass: 47961.910 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: SKP2 N-terminal region not visible in EM density. The LRR region of SKP2 was wholesale docked from previous structure with all sidechains removed. Source: (gene. exp.) Homo sapiens (human) / Gene: SKP2, FBXL1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q13309 |
-Non-polymers , 1 types, 3 molecules
#6: Chemical |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: 2000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 68 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 196974 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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