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Yorodumi- PDB-6w66: The structure of the F64A, S172A mutant Keap1-BTB domain in compl... -
+Open data
-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 | ||||||
Components |
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Keywords | LIGASE/SIGNALING PROTEIN / E3 Ligase / Complex / BTB domain / LIGASE / LIGASE-SIGNALING PROTEIN complex | ||||||
Function / homology | Function and homology information F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of smoothened signaling pathway / neural crest cell differentiation / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ...F-box domain binding / PcG protein complex / regulation of epidermal cell differentiation / Cul7-RING ubiquitin ligase complex / positive regulation of ubiquitin protein ligase activity / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of smoothened signaling pathway / neural crest cell differentiation / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Nuclear events mediated by NFE2L2 / SCF ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / protein quality control for misfolded or incompletely synthesized proteins / entrainment of circadian clock by photoperiod / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / centriolar satellite / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / inclusion body / cellular response to interleukin-4 / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / SCF-beta-TrCP mediated degradation of Emi1 / regulation of autophagy / NIK-->noncanonical NF-kB signaling / molecular function activator activity / actin filament / 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 / 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 / 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 / protein polyubiquitination / Orc1 removal from chromatin / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / KEAP1-NFE2L2 pathway / disordered domain specific binding / Regulation of PLK1 Activity at G2/M Transition / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Circadian Clock / Downstream TCR signaling / cellular response to oxidative stress / Neddylation / nervous system development / midbody / 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 / protein ubiquitination / Ub-specific processing proteases / chromatin remodeling / protein domain specific binding / centrosome / endoplasmic reticulum / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.21 Å | ||||||
Authors | Mena, E.L. / Gee, C.L. / Kuriyan, J. / Rape, M. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nature / Year: 2020 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6w66.cif.gz | 174.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6w66.ent.gz | 110.7 KB | Display | PDB format |
PDBx/mmJSON format | 6w66.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w6/6w66 ftp://data.pdbj.org/pub/pdb/validation_reports/w6/6w66 | HTTPS FTP |
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-Related structure data
Related structure data | 6w67C 6w68C 6w69C 6wcqC 1fqvS 2assS 4cxiS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human) / Gene: SKP1, EMC19, OCP2, SKP1A, TCEB1L / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): LOBSTR / References: UniProt: P63208 |
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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.) Homo sapiens (human) / Gene: FBXL17, FBL17, FBX13, FBXO13 / Cell line (production host): High Five / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UF56 |
#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.) Homo sapiens (human) / Gene: KEAP1, INRF2, KIAA0132, KLHL19 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): LOBSTR / References: UniProt: Q14145 |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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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: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.11583 Å | ||||||||||||||||||||||||||||||
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: molecular replacement | |||||||||
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Phasing MR |
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-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT 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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