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Yorodumi- EMDB-12037: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 s... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12037 | |||||||||
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Title | Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH1. Transition State 1 | |||||||||
Map data | TS1 SCF SKP2- Composite map | |||||||||
Sample |
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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 / cell cycle phase transition / FOXO-mediated transcription of cell cycle genes / negative regulation of epithelial cell proliferation involved in prostate gland development / ubiquitin-protein transferase activator activity / F-box domain binding / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / cyclin A2-CDK1 complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / PcG protein complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / 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 / negative regulation of phosphorylation / mitotic cell cycle phase transition / negative regulation of epithelial cell apoptotic process / negative regulation of cyclin-dependent protein serine/threonine kinase activity / ubiquitin ligase activator activity / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of proteolysis / positive regulation of ubiquitin protein ligase activity / maintenance of protein location in nucleus / cyclin-dependent protein serine/threonine kinase inhibitor activity / protein K11-linked ubiquitination / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / cellular response to leptin stimulus / nuclear export / RHO GTPases activate CIT / positive regulation of protein autoubiquitination / protein neddylation / male pronucleus / ubiquitin conjugating enzyme binding / female pronucleus / cyclin-dependent protein serine/threonine kinase activator activity / cellular response to glucocorticoid stimulus / positive regulation of ubiquitin-protein transferase activity / cellular response to cocaine / response to glucagon / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / AKT phosphorylates targets in the cytosol / ubiquitin-ubiquitin ligase activity / positive regulation of protein targeting to mitochondrion / cyclin-dependent protein serine/threonine kinase regulator activity / cellular response to insulin-like growth factor stimulus / E2 ubiquitin-conjugating enzyme / Cul4A-RING E3 ubiquitin ligase complex / epithelial cell apoptotic process / Cul2-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / cellular response to antibiotic / positive regulation of intracellular estrogen receptor signaling pathway / negative regulation of type I interferon production / negative regulation of kinase activity / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / positive regulation of DNA biosynthetic process / Cul3-RING ubiquitin ligase complex / cellular response to steroid hormone stimulus / cochlea development / molecular function inhibitor activity / protein kinase inhibitor activity / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cellular response to platelet-derived growth factor stimulus / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / cyclin-dependent protein kinase activity / cellular response to lithium ion / Y chromosome / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation / Prolactin receptor signaling / p53-Dependent G1 DNA Damage Response / X chromosome / PTK6 Regulates Cell Cycle / ubiquitin conjugating enzyme activity / regulation of cyclin-dependent protein serine/threonine kinase activity / protein monoubiquitination Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 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_12037.map.gz | 75.5 MB | EMDB map data format | |
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Header (meta data) | emd-12037-v30.xml emd-12037.xml | 27.8 KB 27.8 KB | Display Display | EMDB header |
Images | emd_12037.png | 39.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12037 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12037 | HTTPS FTP |
-Related structure data
Related structure data | 7b5lMC 7b5mC 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_12037.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | TS1 SCF SKP2- Composite map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Sample components
+Entire : NEDD8-CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH...
+Supramolecule #1: NEDD8-CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH...
+Supramolecule #2: NEDD8-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH1. Transit...
+Supramolecule #3: Cullin-1, E3 ubiquitin-protein ligase RBX1
+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: NEDD8
+Macromolecule #8: E3 ubiquitin-protein ligase RBX1
+Macromolecule #9: Ubiquitin-conjugating enzyme E2 L3
+Macromolecule #10: Cyclin-dependent kinase 2
+Macromolecule #11: Cyclin-A2
+Macromolecule #12: Cyclin-dependent kinase inhibitor 1B
+Macromolecule #13: ZINC ION
+Macromolecule #14: 5-azanylpentan-2-one
-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 |
-Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: OTHER / Number images used: 623409 |