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Yorodumi- EMDB-10585: Ubiquitin Ligation to substrate by a cullin-RING E3 ligase at 3.7... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-10585 | |||||||||
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Title | Ubiquitin Ligation to substrate by a cullin-RING E3 ligase at 3.7A resolution: NEDD8-CUL1-RBX1 N98R-SKP1-monomeric b-TRCP1dD-IkBa-UB~UBE2D2 | |||||||||
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Function / homology | Function and homology information I-kappaB/NF-kappaB complex / protein phosphorylated amino acid binding / cytoplasmic sequestering of NF-kappaB / Parkin-FBXW7-Cul1 ubiquitin ligase complex / negative regulation of myeloid cell differentiation / F-box domain binding / nucleotide-binding oligomerization domain containing 1 signaling pathway / IkBA variant leads to EDA-ID / PcG protein complex / (E3-independent) E2 ubiquitin-conjugating enzyme ...I-kappaB/NF-kappaB complex / protein phosphorylated amino acid binding / cytoplasmic sequestering of NF-kappaB / Parkin-FBXW7-Cul1 ubiquitin ligase complex / negative regulation of myeloid cell differentiation / F-box domain binding / nucleotide-binding oligomerization domain containing 1 signaling pathway / IkBA variant leads to EDA-ID / PcG protein complex / (E3-independent) E2 ubiquitin-conjugating enzyme / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / molecular sequestering activity / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / RIP-mediated NFkB activation via ZBP1 / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / SUMOylation of immune response proteins / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of proteolysis / positive regulation of circadian rhythm / maintenance of protein location in nucleus / nucleotide-binding oligomerization domain containing 2 signaling pathway / positive regulation of protein autoubiquitination / protein neddylation / transcription regulator inhibitor activity / regulation of canonical Wnt signaling pathway / branching involved in mammary gland duct morphogenesis / negative regulation of macrophage derived foam cell differentiation / NEDD8 ligase activity / negative regulation of lipid storage / regulation of canonical NF-kappaB signal transduction / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / cellular response to cold / interleukin-1-mediated signaling pathway / mammary gland epithelial cell proliferation / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / non-canonical NF-kappaB signal transduction / Cul2-RING ubiquitin ligase complex / toll-like receptor 4 signaling pathway / ubiquitin ligase complex scaffold activity / Cul4B-RING E3 ubiquitin ligase complex / nuclear localization sequence binding / negative regulation of type I interferon production / positive regulation of cholesterol efflux / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / negative regulation of NF-kappaB transcription factor activity / negative regulation of T cell receptor signaling pathway / Cul3-RING ubiquitin ligase complex / E2 ubiquitin-conjugating enzyme / negative regulation of Notch signaling pathway / response to exogenous dsRNA / Prolactin receptor signaling / ligase activity / protein monoubiquitination / TGF-beta receptor signaling activates SMADs / cullin family protein binding / ubiquitin conjugating enzyme activity / transcription factor binding / response to muramyl dipeptide / TRAF6 mediated NF-kB activation / positive regulation of proteolysis / cellular response to organic cyclic compound / NF-kappaB binding / ubiquitin-like ligase-substrate adaptor activity / anatomical structure morphogenesis / positive regulation of transcription initiation by RNA polymerase II / protein K48-linked ubiquitination / protein autoubiquitination / post-translational protein modification / Nuclear events stimulated by ALK signaling in cancer / regulation of cellular response to insulin stimulus / canonical NF-kappaB signal transduction / regulation of proteasomal protein catabolic process / ubiquitin ligase complex / negative regulation of smoothened signaling pathway / negative regulation of canonical NF-kappaB signal transduction / lipopolysaccharide-mediated signaling pathway / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Notch signaling pathway / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / tumor necrosis factor-mediated signaling pathway / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation Similarity search - Function | |||||||||
Biological species | Pan troglodytes (chimpanzee) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Baek K / Prabu JR / Schulman BA | |||||||||
Funding support | Germany, 1 items
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Citation | Journal: Nature / Year: 2020 Title: NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly. Authors: Kheewoong Baek / David T Krist / J Rajan Prabu / Spencer Hill / Maren Klügel / Lisa-Marie Neumaier / Susanne von Gronau / Gary Kleiger / Brenda A Schulman / Abstract: Eukaryotic cell biology depends on cullin-RING E3 ligase (CRL)-catalysed protein ubiquitylation, which is tightly controlled by the modification of cullin with the ubiquitin-like protein NEDD8. ...Eukaryotic cell biology depends on cullin-RING E3 ligase (CRL)-catalysed protein ubiquitylation, which is tightly controlled by the modification of cullin with the ubiquitin-like protein NEDD8. However, how CRLs catalyse ubiquitylation, and the basis of NEDD8 activation, remain unknown. Here we report the cryo-electron microscopy structure of a chemically trapped complex that represents the ubiquitylation intermediate, in which the neddylated CRL1 promotes the transfer of ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D to its recruited substrate, phosphorylated IκBα. NEDD8 acts as a nexus that binds disparate cullin elements and the RING-activated ubiquitin-linked UBE2D. Local structural remodelling of NEDD8 and large-scale movements of CRL domains converge to juxtapose the substrate and the ubiquitylation active site. These findings explain how a distinctive ubiquitin-like protein alters the functions of its targets, and show how numerous NEDD8-dependent interprotein interactions and conformational changes synergistically configure a catalytic CRL architecture that is both robust, to enable rapid ubiquitylation of the substrate, and fragile, to enable the subsequent functions of cullin-RING proteins. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_10585.map.gz | 8.1 MB | EMDB map data format | |
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Header (meta data) | emd-10585-v30.xml emd-10585.xml | 30 KB 30 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_10585_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_10585.png | 157.1 KB | ||
Masks | emd_10585_msk_1.map | 125 MB | Mask map | |
Others | emd_10585_additional.map.gz emd_10585_half_map_1.map.gz emd_10585_half_map_2.map.gz | 7.6 MB 98.7 MB 98.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-10585 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-10585 | HTTPS FTP |
-Validation report
Summary document | emd_10585_validation.pdf.gz | 406.2 KB | Display | EMDB validaton report |
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Full document | emd_10585_full_validation.pdf.gz | 405.4 KB | Display | |
Data in XML | emd_10585_validation.xml.gz | 17 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10585 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10585 | HTTPS FTP |
-Related structure data
Related structure data | 6ttuMC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_10585.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_10585_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Focused Refinement masking out C/R domain
File | emd_10585_additional.map | ||||||||||||
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Annotation | Focused Refinement masking out C/R domain | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_10585_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_10585_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Ubiquitin Ligation to substrate by a cullin-RING E3 ligase at 3.7...
+Supramolecule #1: Ubiquitin Ligation to substrate by a cullin-RING E3 ligase at 3.7...
+Supramolecule #2: S-phase kinase-associated protein 1
+Supramolecule #3: Cullin-1, E3 ubiquitin-protein ligase RBX1
+Supramolecule #4: F-box/WD repeat-containing protein 1A, NEDD8, S-phase kinase-asso...
+Supramolecule #5: Synthetic peptide
+Macromolecule #1: F-box/WD repeat-containing protein 1A
+Macromolecule #2: S-phase kinase-associated protein 1
+Macromolecule #3: Cullin-1
+Macromolecule #4: NEDD8
+Macromolecule #5: E3 ubiquitin-protein ligase RBX1
+Macromolecule #6: Ubiquitin-conjugating enzyme E2 D2
+Macromolecule #7: Polyubiquitin-C
+Macromolecule #8: CYS-LYS-LYS-ALA-ARG-HIS-ASP-SEP-GLY
+Macromolecule #9: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.8 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 70.2 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |