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- PDB-7b5l: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 s... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7b5l | |||||||||
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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 | |||||||||
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![]() | LIGASE / ubiquitin / ubiquitin ligase / E3 ligase / F-box protein / RBR ligase / Cullin-RING-Ligase / CRL / SCF / NEDD8 / Post-translational modification / ubiquitylation | |||||||||
Function / homology | ![]() 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 / cell cycle phase transition / RBR-type E3 ubiquitin transferase / FOXO-mediated transcription of cell cycle genes / negative regulation of epithelial cell proliferation involved in prostate gland development / F-box domain binding / ubiquitin-protein transferase activator activity / 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 / mitotic cell cycle phase transition / 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 / ubiquitin ligase activator activity / negative regulation of phosphorylation / Cul7-RING ubiquitin ligase complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / 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 / protein K11-linked ubiquitination / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of proteolysis / maintenance of protein location in nucleus / cellular response to leptin stimulus / positive regulation of protein autoubiquitination / protein neddylation / RHO GTPases activate CIT / male pronucleus / cyclin-dependent protein serine/threonine kinase activator activity / female pronucleus / nuclear export / ubiquitin conjugating enzyme binding / cellular response to glucocorticoid stimulus / cellular response to cocaine / response to glucagon / 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 intracellular estrogen receptor signaling pathway / AKT phosphorylates targets in the cytosol / positive regulation of protein targeting to mitochondrion / ubiquitin-ubiquitin ligase activity / cyclin-dependent protein serine/threonine kinase regulator activity / Cul4A-RING E3 ubiquitin ligase complex / epithelial cell apoptotic process / cellular response to insulin-like growth factor stimulus / SCF ubiquitin ligase complex / cellular response to antibiotic / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of kinase activity / E2 ubiquitin-conjugating enzyme / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / cellular response to steroid hormone stimulus / positive regulation of DNA biosynthetic process / regulation of cyclin-dependent protein serine/threonine kinase activity / molecular function inhibitor activity / cochlea development / cellular response to lithium ion / RSV-host interactions / 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 / protein kinase inhibitor activity / Y chromosome / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / Prolactin receptor signaling / X chromosome / PTK6 Regulates Cell Cycle Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Horn-Ghetko, D. / Prabu, J.R. / Schulman, B.A. | |||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 493.9 KB | Display | ![]() |
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PDB format | ![]() | 401.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 813.5 KB | Display | ![]() |
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Full document | ![]() | 864.1 KB | Display | |
Data in XML | ![]() | 77.3 KB | Display | |
Data in CIF | ![]() | 116.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 12037MC ![]() 7b5mC ![]() 7b5nC ![]() 7b5rC ![]() 7b5sC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 6 types, 6 molecules CKUNDY
#1: Protein | Mass: 89800.367 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#4: Protein | Mass: 8968.261 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#6: Protein | Mass: 8519.778 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#7: Protein | Mass: 8573.978 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#9: Protein | Mass: 17825.459 Da / Num. of mol.: 1 / Mutation: C17A, C137A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P68036, E2 ubiquitin-conjugating enzyme |
#11: Protein | Mass: 48609.574 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-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.) ![]() ![]() ![]() References: UniProt: Q9Y4X5, RBR-type E3 ubiquitin transferase |
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#8: Protein | Mass: 12289.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase |
-S-phase kinase-associated protein ... , 2 types, 2 molecules TS
#3: Protein | Mass: 47817.785 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#5: Protein | Mass: 18679.965 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Cyclin-dependent kinase ... , 2 types, 2 molecules LP
#10: Protein | Mass: 34056.469 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#12: Protein | Mass: 22188.303 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: misaligned sequence / Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 2 types, 10 molecules ![](data/chem/img/ZN.gif)
![](data/chem/img/SY8.gif)
![](data/chem/img/SY8.gif)
#13: Chemical | ChemComp-ZN / #14: 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 |
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Sample preparation
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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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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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: 3.8 Å / Resolution method: OTHER / Num. of particles: 623409 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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