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Yorodumi- EMDB-18657: PROTAC-mediated complex of KRAS with VHL/Elongin-B/Elongin-C/Cull... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18657 | |||||||||
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Title | PROTAC-mediated complex of KRAS with VHL/Elongin-B/Elongin-C/Cullin-2/Rbx1 | |||||||||
Map data | sharpened by deepemhancer | |||||||||
Sample |
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Keywords | TARGETED PROTEIN DEGRADATION / PROTAC / GTPASE / TRANSFERASE | |||||||||
Function / homology | Function and homology information regulation of cellular response to hypoxia / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / RHOBTB3 ATPase cycle / cullin-RING ubiquitin ligase complex / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ...regulation of cellular response to hypoxia / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / RHOBTB3 ATPase cycle / cullin-RING ubiquitin ligase complex / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / protein neddylation / Replication of the SARS-CoV-1 genome / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / forebrain astrocyte development / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / intracellular non-membrane-bounded organelle / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of epithelial cell differentiation / ubiquitin ligase complex scaffold activity / regulation of synaptic transmission, GABAergic / epithelial tube branching involved in lung morphogenesis / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / type I pneumocyte differentiation / SUMOylation of ubiquitinylation proteins / Rac protein signal transduction / Prolactin receptor signaling / negative regulation of transcription elongation by RNA polymerase II / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / protein monoubiquitination / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / cullin family protein binding / RAS signaling downstream of NF1 loss-of-function variants / RUNX3 regulates p14-ARF / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / Signalling to RAS / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / SHC-related events triggered by IGF1R / glial cell proliferation / Activated NTRK2 signals through FRS2 and FRS3 / Estrogen-stimulated signaling through PRKCZ / protein K48-linked ubiquitination / Formation of HIV elongation complex in the absence of HIV Tat / Nuclear events stimulated by ALK signaling in cancer / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / negative regulation of signal transduction / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / SHC-mediated cascade:FGFR4 / RNA Polymerase II Transcription Elongation / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / Formation of RNA Pol II elongation complex / protein-membrane adaptor activity / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / positive regulation of glial cell proliferation / homeostasis of number of cells within a tissue / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / p38MAPK events / Tie2 Signaling / FRS-mediated FGFR1 signaling / negative regulation of TORC1 signaling / positive regulation of TORC1 signaling / Signaling by FGFR2 in disease / striated muscle cell differentiation / RNA Polymerase II Pre-transcription Events / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Fischer G / Peter D / Arce-Solano S | |||||||||
Funding support | Austria, 1 items
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Citation | Journal: Biorxiv / Year: 2023 Title: Targeting cancer with small molecule pan-KRAS degraders Authors: Popow J / Farnaby W / Gollner A / Kofink C / Fischer G / Wurm M / Zollman D / Wijaya A / Mischerikow N / Hasenoehrl C / Prokofeva P / Arnhof H / Arce-Solano S / Bell S / Boeck G / Diers E / ...Authors: Popow J / Farnaby W / Gollner A / Kofink C / Fischer G / Wurm M / Zollman D / Wijaya A / Mischerikow N / Hasenoehrl C / Prokofeva P / Arnhof H / Arce-Solano S / Bell S / Boeck G / Diers E / Frost A / Goodwin-Tindall J / Karolyi-Oezguer J / Khan S / Klawatsch T / Koegl M / Kousek R / Kratochvil B / Kropatsch K / Lauber A / McLennan R / Olt S / Peter D / Petermann O / Roessler V / Stolt-Bergner P / Strack P / Strauss E / Trainor N / Vetma V / Whitworth C / Zhong S / Quant J / Weinstabl H / Kuster B / Ettmayer P / Ciulli A | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18657.map.gz | 189 MB | EMDB map data format | |
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Header (meta data) | emd-18657-v30.xml emd-18657.xml | 29.5 KB 29.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18657_fsc.xml | 14.4 KB | Display | FSC data file |
Images | emd_18657.png | 98.1 KB | ||
Filedesc metadata | emd-18657.cif.gz | 7.9 KB | ||
Others | emd_18657_additional_1.map.gz emd_18657_half_map_1.map.gz emd_18657_half_map_2.map.gz | 201.4 MB 3.3 MB 3.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18657 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18657 | HTTPS FTP |
-Validation report
Summary document | emd_18657_validation.pdf.gz | 444.7 KB | Display | EMDB validaton report |
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Full document | emd_18657_full_validation.pdf.gz | 444.3 KB | Display | |
Data in XML | emd_18657_validation.xml.gz | 21.6 KB | Display | |
Data in CIF | emd_18657_validation.cif.gz | 28.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18657 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18657 | HTTPS FTP |
-Related structure data
Related structure data | 8qu8MC 8qugC 8qvuC 8qw6C 8qw7C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18657.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | sharpened by deepemhancer | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.99333 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: unsharpened map from 3D flex
File | emd_18657_additional_1.map | ||||||||||||
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Annotation | unsharpened map from 3D flex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_18657_half_map_1.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_18657_half_map_2.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : KRAS/ACBI3/VHL/EloB/EloC/Cul2/Rbx1
+Supramolecule #1: KRAS/ACBI3/VHL/EloB/EloC/Cul2/Rbx1
+Macromolecule #1: von Hippel-Lindau disease tumor suppressor
+Macromolecule #2: Elongin-B
+Macromolecule #3: Elongin-C
+Macromolecule #4: Cullin-2
+Macromolecule #5: E3 ubiquitin-protein ligase RBX1, N-terminally processed
+Macromolecule #6: GTPase KRas
+Macromolecule #7: ZINC ION
+Macromolecule #8: GUANOSINE-5'-DIPHOSPHATE
+Macromolecule #9: (2S,4R)-1-[(2S)-2-[4-[4-[(3S)-4-[4-[5-[(4S)-2-azanyl-3-cyano-4-me...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.916 mg/mL | ||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. / Pretreatment - Atmosphere: AIR | ||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris / Energy filter - Slit width: 10 eV |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 7634 / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 165000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |