+
Open data
-
Basic information
Entry | Database: PDB / ID: 6wcq | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of a substrate-bound DQC ubiquitin ligase | ||||||
![]() |
| ||||||
![]() | LIGASE / ubiquitin / E3-ligase / multiprotein complex / substrate recognition | ||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 8.5 Å | ||||||
![]() | Mena, E.L. / Jevtic, P. / Greber, B.J. / Gee, C.L. / Lew, B.G. / Akopian, D. / Nogales, E. / Kuriyan, J. / Rape, M. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() 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 |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 201.9 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 144.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 976 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 990.9 KB | Display | |
Data in XML | ![]() | 34.4 KB | Display | |
Data in CIF | ![]() | 51 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 21617MC ![]() 6w66C ![]() 6w67C ![]() 6w68C ![]() 6w69C C: citing same article ( M: map data used to model this data |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 18679.965 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
---|---|
#2: Protein | Mass: 44970.043 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Protein | Mass: 70173.484 Da / Num. of mol.: 1 / Mutation: V99A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#4: Protein | Mass: 49926.520 Da / Num. of mol.: 1 / Fragment: residues 1-434 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: CUL1-SKP1-FBXL17-KEAP1 complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | |||||||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | |||||||||||||||||||||||||||||||||||
Buffer solution |
| |||||||||||||||||||||||||||||||||||
Buffer component |
| |||||||||||||||||||||||||||||||||||
Specimen |
| |||||||||||||||||||||||||||||||||||
Specimen support |
| |||||||||||||||||||||||||||||||||||
Vitrification |
|
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM imaging | Accelerating voltage: 200 kV / Alignment procedure: COMA FREE / C2 aperture diameter: 50 µm / Cryogen: NITROGEN / Electron source:
| ||||||||||||||||||
Image recording |
|
-
Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Image processing | Details: Datasets from K3 and K2 were joined for the final reconstruction. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CTF correction | Details: As implemented in RELION. / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 824561 Details: Total number of particles for both datasets. Selected using RELION auto-picking (Laplacian-of-Gaussian). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 8.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 160256 / Algorithm: FOURIER SPACE / Num. of class averages: 2 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL Details: Coordinates were fitted as rigid bodies or fragments in Chimera and subsequently geometry-optimized using PHENIX real space refinement. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|