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- PDB-6w66: The structure of the F64A, S172A mutant Keap1-BTB domain in compl... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6w66 | ||||||
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Title | The structure of the F64A, S172A mutant Keap1-BTB domain in complex with SKP1-FBXL17 | ||||||
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![]() | LIGASE/SIGNALING PROTEIN / E3 Ligase / Complex / BTB domain / LIGASE / LIGASE-SIGNALING PROTEIN complex | ||||||
Function / homology | ![]() F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / 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 ...F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / 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 / 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 / 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 / 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 / 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 / in utero embryonic development / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / Ub-specific processing proteases / protein ubiquitination / chromatin remodeling / protein domain specific binding / centrosome / endoplasmic reticulum / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() ![]() | ||||||
![]() | Mena, E.L. / Gee, C.L. / Kuriyan, J. / Rape, M. | ||||||
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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 174.3 KB | Display | ![]() |
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PDB format | ![]() | 110.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 444.7 KB | Display | ![]() |
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Full document | ![]() | 450.4 KB | Display | |
Data in XML | ![]() | 23.6 KB | Display | |
Data in CIF | ![]() | 31.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6w67C ![]() 6w68C ![]() 6w69C ![]() 6wcqC ![]() 1fqvS ![]() 2assS ![]() 4cxiS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 18679.965 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 44970.043 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Protein | Mass: 14861.131 Da / Num. of mol.: 1 / Fragment: BTB domain / Mutation: F64A/S172A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.43 Å3/Da / Density % sol: 64.16 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop Details: well solution 37.5 ul of 50 mM MgCl2, 100 mM HEPES pH 7.5, 30% (v/v) PEG MME 550 (E7 Hampton Index) + 12.5ul H2O mixed 1:1 with complex at 15mg/ml in 150 mM NaCl, 25 mM Tris/HCl pH 8.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 3, 2018 | ||||||||||||||||||||||||||||||
Radiation | Monochromator: S111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.11583 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 3.21→159.06 Å / Num. obs: 17752 / % possible obs: 99.6 % / Redundancy: 10.6 % / Biso Wilson estimate: 101.91 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.289 / Rpim(I) all: 0.093 / Rrim(I) all: 0.304 / Net I/σ(I): 7.6 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: ![]() | |||||||||
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Phasing MR |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4CXI, 2ASS, 1FQV Resolution: 3.21→79.53 Å / SU ML: 0.4835 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 37.2992
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 119.12 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.21→79.53 Å
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Refine LS restraints |
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LS refinement shell |
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