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Yorodumi- EMDB-12041: Focused map-catalytic side. Ubiquitin ligation to F-box protein s... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12041 | |||||||||
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Title | Focused map-catalytic side. Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-UBE2L3~Ub~ARIH1. | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cell cycle phase transition / RBR-type E3 ubiquitin transferase / ubiquitin-protein transferase activator activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity ...PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cell cycle phase transition / RBR-type E3 ubiquitin transferase / ubiquitin-protein transferase activator activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / 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 / protein K11-linked ubiquitination / regulation of proteolysis / positive regulation of protein autoubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / cellular response to glucocorticoid stimulus / NEDD8 ligase activity / positive regulation of ubiquitin-protein transferase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / positive regulation of protein targeting to mitochondrion / 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 / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / E2 ubiquitin-conjugating enzyme / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / cellular response to steroid hormone stimulus / RSV-host interactions / Prolactin receptor signaling / TGF-beta receptor signaling activates SMADs / protein monoubiquitination / ubiquitin conjugating enzyme activity / cullin family protein binding / anatomical structure morphogenesis / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / Cajal body / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / 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 / Membrane binding and targetting of GAG proteins / positive regulation of TORC1 signaling / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / T cell activation / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / intrinsic apoptotic signaling pathway / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / post-translational protein modification / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 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_12041.map.gz | 9.1 MB | EMDB map data format | |
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Header (meta data) | emd-12041-v30.xml emd-12041.xml | 26.9 KB 26.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_12041_fsc.xml | 11.4 KB | Display | FSC data file |
Images | emd_12041.png | 46.2 KB | ||
Masks | emd_12041_msk_1.map | 125 MB | Mask map | |
Others | emd_12041_additional_1.map.gz emd_12041_half_map_1.map.gz emd_12041_half_map_2.map.gz | 7.5 MB 98.4 MB 98.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12041 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12041 | HTTPS FTP |
-Validation report
Summary document | emd_12041_validation.pdf.gz | 326.2 KB | Display | EMDB validaton report |
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Full document | emd_12041_full_validation.pdf.gz | 325.4 KB | Display | |
Data in XML | emd_12041_validation.xml.gz | 17.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12041 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12041 | HTTPS FTP |
-Related structure data
Related structure data | 7b5nMC 7b5lC 7b5mC 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_12041.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: 1.09 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_12041_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_12041_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_12041_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_12041_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-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: CUL1, RBX1
+Macromolecule #1: Cullin-1
+Macromolecule #2: E3 ubiquitin-protein ligase ARIH1
+Macromolecule #3: Polyubiquitin-C
+Macromolecule #4: NEDD8
+Macromolecule #5: E3 ubiquitin-protein ligase RBX1
+Macromolecule #6: Ubiquitin-conjugating enzyme E2 L3
+Macromolecule #7: ZINC ION
+Macromolecule #8: 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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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 |