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Yorodumi- EMDB-12040: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 s... -
+Open data
-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 / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / autophagic cell death / 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 / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / autophagic cell death / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / FOXO-mediated transcription of cell cycle genes / negative regulation of epithelial cell proliferation involved in prostate gland development / F-box domain binding / RBR-type E3 ubiquitin transferase / Aberrant regulation of mitotic exit in cancer due to RB1 defects / PcG protein complex / regulation of cell cycle G1/S phase transition / negative regulation of phosphorylation / regulation of exit from mitosis / cullin-RING-type E3 NEDD8 transferase / mitotic cell cycle phase transition / cellular response to chemical stress / NEDD8 transferase activity / epithelial cell proliferation involved in prostate gland development / cullin-RING ubiquitin ligase complex / negative regulation of epithelial cell apoptotic process / negative regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of ubiquitin protein ligase activity / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / ubiquitin ligase activator activity / Cul7-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / cyclin-dependent protein serine/threonine kinase inhibitor activity / positive regulation of protein autoubiquitination / RHO GTPases activate CIT / protein neddylation / ubiquitin conjugating enzyme binding / cyclin-dependent protein serine/threonine kinase activator activity / nuclear export / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / AKT phosphorylates targets in the cytosol / positive regulation of intracellular estrogen receptor signaling pathway / ubiquitin-ubiquitin ligase activity / epithelial cell apoptotic process / SCF ubiquitin ligase complex / cellular response to antibiotic / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4B-RING E3 ubiquitin ligase complex / Cul3-RING ubiquitin ligase complex / molecular function inhibitor activity / negative regulation of kinase activity / regulation of cyclin-dependent protein serine/threonine kinase activity / cellular response to lithium ion / RSV-host interactions / p53-Dependent G1 DNA Damage Response / protein kinase inhibitor activity / Prolactin receptor signaling / PTK6 Regulates Cell Cycle / regulation of G1/S transition of mitotic cell cycle / protein monoubiquitination / Constitutive Signaling by AKT1 E17K in Cancer / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / negative regulation of vascular associated smooth muscle cell proliferation / cullin family protein binding / inner ear development / protein K63-linked ubiquitination / cellular response to organic cyclic compound / negative regulation of mitotic cell cycle / positive regulation of double-strand break repair via homologous recombination / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / ubiquitin-like ligase-substrate adaptor activity / response to amino acid / protein K48-linked ubiquitination / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / response to cadmium ion / response to glucose / Cajal body / Nuclear events stimulated by ALK signaling in cancer / Cyclin E associated events during G1/S transition / cyclin-dependent protein kinase holoenzyme complex / Cyclin A:Cdk2-associated events at S phase entry / ubiquitin ligase complex / Maturation of protein E / Notch signaling pathway / Maturation of protein E / ER Quality Control Compartment (ERQC) / regulation of mitotic cell cycle / Myoclonic epilepsy of Lafora / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / FLT3 signaling by CBL mutants / positive regulation of microtubule polymerization / IRAK1 recruits IKK complex 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 |
-Validation report
Summary document | emd_12040_validation.pdf.gz | 317.8 KB | Display | EMDB validaton report |
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Full document | emd_12040_full_validation.pdf.gz | 316.9 KB | Display | |
Data in XML | emd_12040_validation.xml.gz | 16.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12040 ftp://ftp.pdbj.org/pub/emdb/validation_reports/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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 70.0 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 |