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Yorodumi- EMDB-12040: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 s... -
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-Basic information
Entry | Database: EMDB / ID: EMD-12040 | |||||||||
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Title | Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-SKP1-SKP2-CKSHS1-p27~Ub~ARIH1. Transition State 2 | |||||||||
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Function / homology | Function and homology information PKR/eIFalpha signaling / cyclin-dependent protein kinase activating kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cardiac muscle tissue regeneration / negative regulation of cyclin-dependent protein kinase activity / autophagic cell death / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex ...PKR/eIFalpha signaling / cyclin-dependent protein kinase activating kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cardiac muscle tissue regeneration / negative regulation of cyclin-dependent protein kinase activity / autophagic cell death / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / RBR-type E3 ubiquitin transferase / negative regulation of epithelial cell proliferation involved in prostate gland development / FOXO-mediated transcription of cell cycle genes / F-box domain binding / Aberrant regulation of mitotic exit in cancer due to RB1 defects / PcG protein complex / regulation of cell cycle G1/S phase transition / regulation of exit from mitosis / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / epithelial cell proliferation involved in prostate gland development / cullin-RING ubiquitin ligase complex / mitotic cell cycle phase transition / negative regulation of epithelial cell apoptotic process / negative regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of phosphorylation / ubiquitin ligase activator activity / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / positive regulation of ubiquitin protein ligase activity / cyclin-dependent protein serine/threonine kinase inhibitor activity / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / positive regulation of protein autoubiquitination / RHO GTPases activate CIT / protein neddylation / cyclin-dependent protein serine/threonine kinase activator activity / nuclear export / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / AKT phosphorylates targets in the cytosol / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / epithelial cell apoptotic process / SCF ubiquitin ligase complex / cellular response to antibiotic / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / positive regulation of intracellular estrogen receptor signaling pathway / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of kinase activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / cellular response to lithium ion / molecular function inhibitor activity / protein kinase inhibitor activity / p53-Dependent G1 DNA Damage Response / Prolactin receptor signaling / PTK6 Regulates Cell Cycle / regulation of cyclin-dependent protein serine/threonine kinase activity / Constitutive Signaling by AKT1 E17K in Cancer / regulation of G1/S transition of mitotic cell cycle / protein monoubiquitination / negative regulation of vascular associated smooth muscle cell proliferation / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / cullin family protein binding / inner ear development / cellular response to organic cyclic compound / ubiquitin-like ligase-substrate adaptor activity / negative regulation of mitotic cell cycle / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / cyclin-dependent protein kinase holoenzyme complex / Nuclear events stimulated by ALK signaling in cancer / response to amino acid / localization / protein K48-linked ubiquitination / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Cajal body / response to glucose / response to cadmium ion / Cyclin E associated events during G1/S transition / Cyclin A:Cdk2-associated events at S phase entry / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / positive regulation of microtubule polymerization / ER Quality Control Compartment (ERQC) / regulation of cell migration / Myoclonic epilepsy of Lafora / Notch signaling pathway / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.91 Å | |||||||||
Authors | Horn-Ghetko D / Prabu JR / Schulman BA | |||||||||
Funding support | Germany, 2 items
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Citation | Journal: Nature / Year: 2021 Title: Ubiquitin ligation to F-box protein targets by SCF-RBR E3-E3 super-assembly. Authors: Daniel Horn-Ghetko / David T Krist / J Rajan Prabu / Kheewoong Baek / Monique P C Mulder / Maren Klügel / Daniel C Scott / Huib Ovaa / Gary Kleiger / Brenda A Schulman / Abstract: E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates. However, rather ...E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates. However, rather than functioning individually, many neddylated cullin-RING E3 ligases (CRLs) and RBR-type E3 ligases in the ARIH family-which together account for nearly half of all ubiquitin ligases in humans-form E3-E3 super-assemblies. Here, by studying CRLs in the SKP1-CUL1-F-box (SCF) family, we show how neddylated SCF ligases and ARIH1 (an RBR-type E3 ligase) co-evolved to ubiquitylate diverse substrates presented on various F-box proteins. We developed activity-based chemical probes that enabled cryo-electron microscopy visualization of steps in E3-E3 ubiquitylation, initiating with ubiquitin linked to the E2 enzyme UBE2L3, then transferred to the catalytic cysteine of ARIH1, and culminating in ubiquitin linkage to a substrate bound to the SCF E3 ligase. The E3-E3 mechanism places the ubiquitin-linked active site of ARIH1 adjacent to substrates bound to F-box proteins (for example, substrates with folded structures or limited length) that are incompatible with previously described conventional RING E3-only mechanisms. The versatile E3-E3 super-assembly may therefore underlie widespread ubiquitylation. | |||||||||
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_12040.map.gz | 9.1 MB | EMDB map data format | |
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Header (meta data) | emd-12040-v30.xml emd-12040.xml | 27 KB 27 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_12040_fsc.xml | 11.1 KB | Display | FSC data file |
Images | emd_12040.png | 95.3 KB | ||
Masks | emd_12040_msk_1.map | 115.9 MB | Mask map | |
Others | emd_12040_half_map_1.map.gz emd_12040_half_map_2.map.gz | 91.1 MB 91 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12040 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12040 | HTTPS FTP |
-Related structure data
Related structure data | 7b5mMC 7b5lC 7b5nC 7b5rC 7b5sC 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_12040.map.gz / Format: CCP4 / Size: 115.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.09 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_12040_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_12040_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_12040_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : CUL1-RBX1-SKP1-SKP2-CKSHS1-p27~Ub~ARIH1
+Supramolecule #1: CUL1-RBX1-SKP1-SKP2-CKSHS1-p27~Ub~ARIH1
+Supramolecule #2: Cullin-1, E3 ubiquitin-protein ligase RBX1
+Supramolecule #3: ARIH1, SKP2, CKS1B, SKP1, UBC
+Supramolecule #4: Cyclin-dependent kinase inhibitor 1B
+Macromolecule #1: Cullin-1
+Macromolecule #2: E3 ubiquitin-protein ligase ARIH1
+Macromolecule #3: S-phase kinase-associated protein 2
+Macromolecule #4: Cyclin-dependent kinases regulatory subunit 1
+Macromolecule #5: S-phase kinase-associated protein 1
+Macromolecule #6: Polyubiquitin-C
+Macromolecule #7: E3 ubiquitin-protein ligase RBX1
+Macromolecule #8: Cyclin-dependent kinase inhibitor 1B
+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 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 70.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |