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Yorodumi- PDB-7b5n: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 s... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7b5n | |||||||||
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Title | Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-UBE2L3~Ub~ARIH1. | |||||||||
Components |
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Keywords | LIGASE / ubiquitin / ubiquitin ligase / E3 ligase / F-box protein / RBR ligase / Cullin-RING-Ligase / CRL / SCF / NEDD8 / Post-translational modification / ubiquitylation | |||||||||
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 / regulation of proteolysis / positive regulation of protein autoubiquitination / protein K11-linked ubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / cellular response to glucocorticoid stimulus / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / positive regulation of ubiquitin-protein transferase activity / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / positive regulation of protein targeting to mitochondrion / Cul2-RING ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / cellular response to steroid hormone stimulus / E2 ubiquitin-conjugating enzyme / RSV-host interactions / Prolactin receptor signaling / protein monoubiquitination / TGF-beta receptor signaling activates SMADs / cullin family protein binding / ubiquitin conjugating enzyme activity / 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 / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / 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 / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / positive regulation of TORC1 signaling / T cell activation / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Regulation of pyruvate metabolism / Downregulation of ERBB2:ERBB3 signaling / regulation of cellular response to insulin stimulus / NF-kB is activated and signals survival / Regulation of PTEN localization / NRIF signals cell death from the nucleus / Regulation of BACH1 activity / Activated NOTCH1 Transmits Signal to the Nucleus / intrinsic apoptotic signaling pathway / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / TICAM1, RIP1-mediated IKK complex recruitment / post-translational protein modification / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Horn-Ghetko, D. / Prabu, J.R. / Schulman, B.A. | |||||||||
Funding support | Germany, 2items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7b5n.cif.gz | 237.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7b5n.ent.gz | 189.2 KB | Display | PDB format |
PDBx/mmJSON format | 7b5n.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b5/7b5n ftp://data.pdbj.org/pub/pdb/validation_reports/b5/7b5n | HTTPS FTP |
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-Related structure data
Related structure data | 12041MC 7b5lC 7b5mC 7b5rC 7b5sC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 4 types, 4 molecules CUND
#1: Protein | Mass: 89800.367 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q13616 |
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#3: Protein | Mass: 8519.778 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UBC / Production host: Escherichia coli (E. coli) / References: UniProt: P0CG48 |
#4: Protein | Mass: 9086.562 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NEDD8 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15843 |
#6: Protein | Mass: 17825.459 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UBE2L3, UBCE7, UBCH7 / Production host: Escherichia coli (E. coli) References: UniProt: P68036, E2 ubiquitin-conjugating enzyme |
-E3 ubiquitin-protein ligase ... , 2 types, 2 molecules HR
#2: Protein | Mass: 64197.777 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ARIH1, ARI, MOP6, UBCH7BP, HUSSY-27 / Production host: Escherichia coli (E. coli) References: UniProt: Q9Y4X5, RBR-type E3 ubiquitin transferase |
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#5: Protein | Mass: 12289.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1, RNF75, ROC1 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase |
-Non-polymers , 2 types, 10 molecules
#7: Chemical | ChemComp-ZN / #8: Chemical | ChemComp-SY8 / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Molecular weight | Value: 0.30 MDa | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 623409 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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