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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21617 | |||||||||
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Title | Structure of a substrate-bound DQC ubiquitin ligase | |||||||||
![]() | Unfiltered half-map from RELION auto-refinement | |||||||||
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![]() | ubiquitin / E3-ligase / multiprotein complex / substrate recognition / LIGASE | |||||||||
Function / homology | ![]() Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / 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 / regulation of smoothened signaling pathway ...Parkin-FBXW7-Cul1 ubiquitin ligase complex / F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / 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 / regulation of smoothened signaling pathway / neural crest cell differentiation / negative regulation of response to oxidative stress / Nuclear events mediated by NFE2L2 / SCF 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 quality control for misfolded or incompletely synthesized proteins / entrainment of circadian clock by photoperiod / protein monoubiquitination / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / centriolar satellite / cellular response to interleukin-4 / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / inclusion body / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / MAP3K8 (TPL2)-dependent MAPK1/3 activation / regulation of autophagy / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / molecular function activator activity / Vpu mediated degradation of CD4 / actin filament / 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 / Degradation of beta-catenin by the destruction complex / negative regulation of DNA-binding transcription factor activity / NOTCH1 Intracellular Domain Regulates Transcription / CLEC7A (Dectin-1) signaling / beta-catenin binding / SCF(Skp2)-mediated degradation of p27/p21 / 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 / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / Regulation of PLK1 Activity at G2/M Transition / KEAP1-NFE2L2 pathway / disordered domain specific binding / Circadian Clock / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Downstream TCR signaling / protein-macromolecule adaptor activity / nervous system development / Neddylation / mitotic cell cycle / midbody / cellular response to oxidative stress / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / cell population proliferation / Potential therapeutics for SARS / Ub-specific processing proteases / protein ubiquitination / chromatin remodeling / protein domain specific binding / centrosome / ubiquitin protein ligase binding / endoplasmic reticulum / nucleoplasm / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.5 Å | |||||||||
![]() | Mena EL / Jevtic P | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for dimerization quality control. Authors: Elijah L Mena / Predrag Jevtić / Basil J Greber / Christine L Gee / Brandon G Lew / David Akopian / Eva Nogales / John Kuriyan / Michael Rape / ![]() Abstract: Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration. Dimerization quality control further improves proteostasis by eliminating complexes of ...Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration. Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition, but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF-FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing functional homodimers. We find that SCF-FBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular β-sheet around a highly divergent β-strand of the BTB domain. Complex dissociation allows SCF-FBXL17 to wrap around a single BTB domain, resulting in robust ubiquitylation. SCF-FBXL17 therefore probes both shape and complementarity of BTB domains, a mechanism that is well suited to establish quality control of complex composition for recurrent interaction modules. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 26 KB 26 KB | Display Display | ![]() |
Images | ![]() | 91 KB | ||
Filedesc metadata | ![]() | 7.4 KB | ||
Others | ![]() ![]() | 4 MB 4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 617.9 KB | Display | ![]() |
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Full document | ![]() | 617.4 KB | Display | |
Data in XML | ![]() | 7.9 KB | Display | |
Data in CIF | ![]() | 9.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6wcqMC ![]() 6w66C ![]() 6w67C ![]() 6w68C ![]() 6w69C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Unfiltered half-map from RELION auto-refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.28 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: Unfiltered half-map from RELION auto-refinement
File | emd_21617_half_map_1.map | ||||||||||||
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Annotation | Unfiltered half-map from RELION auto-refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Unfiltered half-map from RELION auto-refinement
File | emd_21617_half_map_2.map | ||||||||||||
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Annotation | Unfiltered half-map from RELION auto-refinement | ||||||||||||
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Density Histograms |
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Sample components
-Entire : CUL1-SKP1-FBXL17-KEAP1 complex
Entire | Name: CUL1-SKP1-FBXL17-KEAP1 complex |
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Components |
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-Supramolecule #1: CUL1-SKP1-FBXL17-KEAP1 complex
Supramolecule | Name: CUL1-SKP1-FBXL17-KEAP1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: S-phase kinase-associated protein 1
Macromolecule | Name: S-phase kinase-associated protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 18.679965 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ WCTHHKDDPP PPEDDENKEK RTDDIPVWD QEFLKVDQGT LFELILAANY LDIKGLLDVT CKTVANMIKG KTPEEIRKTF NIKNDFTEEE EAQVRKENQW C EEK UniProtKB: S-phase kinase-associated protein 1 |
-Macromolecule #2: F-box/LRR-repeat protein 17
Macromolecule | Name: F-box/LRR-repeat protein 17 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 44.970043 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GEFMCHREPP PETPDINQLP PSILLKIFSN LSLDERCLSA SLVCKYWRDL CLDFQFWKQL DLSSRQQVTD ELLEKIASRS QNIIEINIS DCRSMSDNGV CVLAFKCPGL LRYTAYRCKQ LSDTSIIAVA SHCPLLQKVH VGNQDKLTDE GLKQLGSKCR E LKDIHFGQ ...String: GEFMCHREPP PETPDINQLP PSILLKIFSN LSLDERCLSA SLVCKYWRDL CLDFQFWKQL DLSSRQQVTD ELLEKIASRS QNIIEINIS DCRSMSDNGV CVLAFKCPGL LRYTAYRCKQ LSDTSIIAVA SHCPLLQKVH VGNQDKLTDE GLKQLGSKCR E LKDIHFGQ CYKISDEGMI VIAKGCLKLQ RIYMQENKLV TDQSVKAFAE HCPELQYVGF MGCSVTSKGV IHLTKLRNLS SL DLRHITE LDNETVMEIV KRCKNLSSLN LCLNWIINDR CVEVIAKEGQ NLKELYLVSC KITDYALIAI GRYSMTIETV DVG WCKEIT DQGATLIAQS SKSLRYLGLM RCDKVNEVTV EQLVQQYPHI TFSTVLQDCK RTLERAYQMG WTPNMSAASS UniProtKB: F-box/LRR-repeat protein 17 |
-Macromolecule #3: Kelch-like ECH-associated protein 1
Macromolecule | Name: Kelch-like ECH-associated protein 1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 70.173484 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GGGSGGSMQP DPRPSGAGAC CRFLPLQSQC PEGAGDAVMY ASTECKAEVT PSQHGNRTFS YTLEDHTKQA FGIMNELRLS QQLCDVTLQ VKYQDAPAAQ FMAHKVALAS SSPVFKAMFT NGLREQGMEV VSIEGIHPKV MERLIEFAYT ASISMGEKCV L HVMNGAVM ...String: GGGSGGSMQP DPRPSGAGAC CRFLPLQSQC PEGAGDAVMY ASTECKAEVT PSQHGNRTFS YTLEDHTKQA FGIMNELRLS QQLCDVTLQ VKYQDAPAAQ FMAHKVALAS SSPVFKAMFT NGLREQGMEV VSIEGIHPKV MERLIEFAYT ASISMGEKCV L HVMNGAVM YQIDSVVRAC SDFLVQQLDP SNAIGIANFA EQIGCVELHQ RAREYIYMHF GEVAKQEEFF NLSHCQLVTL IS RDDLNVR CESEVFHACI NWVKYDCEQR RFYVQALLRA VRCHSLTPNF LQMQLQKCEI LQSDSRCKDY LVKIFEELTL HKP TQVMPC RAPKVGRLIY TAGGYFRQSL SYLEAYNPSD GTWLRLADLQ VPRSGLAGCV VGGLLYAVGG RNNSPDGNTD SSAL DCYNP MTNQWSPCAP MSVPRNRIGV GVIDGHIYAV GGSHGCIHHN SVERYEPERD EWHLVAPMLT RRIGVGVAVL NRLLY AVGG FDGTNRLNSA ECYYPERNEW RMITAMNTIR SGAGVCVLHN CIYAAGGYDG QDQLNSVERY DVETETWTFV APMKHR RSA LGITVHQGRI YVLGGYDGHT FLDSVECYDP DTDTWSEVTR MTSGRSGVGV AVTMEPCRKQ IDQQNCTC UniProtKB: Kelch-like ECH-associated protein 1 |
-Macromolecule #4: Cullin-1
Macromolecule | Name: Cullin-1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 49.92652 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSSTRSQNPH GLKQIGLDQI WDDLRAGIQQ VYTRQSMAKS RYMELYTHVY NYCTSVHQSN QARGAGVPPS KSKKGQTPGG AQFVGLELY KRLKEFLKNY LTNLLKDGED LMDESVLKFY TQQWEDYRFS SKVLNGICAY LNRHWVRREC DEGRKGIYEI Y SLALVTWR ...String: MSSTRSQNPH GLKQIGLDQI WDDLRAGIQQ VYTRQSMAKS RYMELYTHVY NYCTSVHQSN QARGAGVPPS KSKKGQTPGG AQFVGLELY KRLKEFLKNY LTNLLKDGED LMDESVLKFY TQQWEDYRFS SKVLNGICAY LNRHWVRREC DEGRKGIYEI Y SLALVTWR DCLFRPLNKQ VTNAVLKLIE KERNGETINT RLISGVVQSY VELGLNEDDA FAKGPTLTVY KESFESQFLA DT ERFYTRE STEFLQQNPV TEYMKKAEAR LLEEQRRVQV YLHESTQDEL ARKCEQVLIE KHLEIFHTEF QNLLDADKNE DLG RMYNLV SRIQDGLGEL KKLLETHIHN QGLAAIEKCG EAALNDPKMY VQTVLDVHKK YNALVMSAFN NDAGFVAALD KACG RFINN NAVTKMAQSS SKSPELLARY CDSLLKKSS UniProtKB: Cullin-1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation #1
Preparation ID | 1 | ||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil, UltrAuFoil, R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Film type ID: 1 / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE Details: Glow discharge before deposition of graphene oxide. | ||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||
Details | Crosslinked with BS3 |
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Sample preparation #2
Preparation ID | 2 | ||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil, UltrAuFoil, R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Film type ID: 1 / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE Details: Glow discharge before deposition of graphene oxide. | ||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||
Details | Crosslinked with BS3 |
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Electron microscopy #1
Microscopy ID | 1 |
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Microscope | FEI TALOS ARCTICA |
Image recording | Image recording ID: 1 / Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 2.0 µm |
Sample stage | Specimen holder model: OTHER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Electron microscopy #1~
Microscopy ID | 1 |
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Microscope | FEI TALOS ARCTICA |
Image recording | Image recording ID: 2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 1 / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.5 µm |
Sample stage | Specimen holder model: OTHER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model |
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Details | Coordinates were fitted as rigid bodies or fragments in Chimera and subsequently geometry-optimized using PHENIX real space refinement. | ||||||
Refinement | Space: REAL / Protocol: OTHER | ||||||
Output model | ![]() PDB-6wcq: |