[English] 日本語
Yorodumi- PDB-7b5m: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 s... -
+
Open data
-
Basic information
| Entry | Database: PDB / ID: 7b5m | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 informationPKR/eIFalpha signaling / cyclin-dependent protein kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cyclin-dependent protein kinase activity / negative regulation of cardiac muscle tissue regeneration / negative regulation of kinase activity / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / autophagic cell death / FOXO-mediated transcription of cell cycle genes ...PKR/eIFalpha signaling / cyclin-dependent protein kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cyclin-dependent protein kinase activity / negative regulation of cardiac muscle tissue regeneration / negative regulation of kinase activity / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / autophagic cell death / FOXO-mediated transcription of cell cycle genes / Parkin-FBXW7-Cul1 ubiquitin ligase complex / Lewy body / RBR-type E3 ubiquitin transferase / F-box domain binding / negative regulation of epithelial cell proliferation involved in prostate gland development / negative regulation of cyclin-dependent protein serine/threonine kinase activity / cellular response to cell-matrix adhesion / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of cell cycle G1/S phase transition / PcG protein complex / regulation of exit from mitosis / cullin-RING-type E3 NEDD8 transferase / negative regulation of epithelial cell apoptotic process / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / epithelial cell proliferation involved in prostate gland development / positive regulation of ubiquitin protein ligase activity / cyclin-dependent protein serine/threonine kinase inhibitor activity / cellular response to chemical stress / 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 / maintenance of protein location in nucleus / ubiquitin ligase activator activity / regulation of cyclin-dependent protein serine/threonine kinase activity / RHO GTPases activate CIT / positive regulation of protein autoubiquitination / RNA polymerase II transcription initiation surveillance / protein neddylation / cyclin-dependent protein serine/threonine kinase activator activity / nuclear export / negative regulation of mitotic cell cycle / ubiquitin conjugating enzyme binding / Modulation of host responses by IFN-stimulated genes / NEDD8 ligase activity / AKT phosphorylates targets in the cytosol / VCB complex / epithelial cell apoptotic process / negative regulation of response to oxidative stress / Cul5-RING ubiquitin ligase complex / cellular response to antibiotic / SCF ubiquitin ligase complex / negative regulation of type I interferon production / Cul2-RING ubiquitin ligase complex / ubiquitin-ubiquitin ligase activity / molecular function inhibitor activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / cellular response to lithium ion / Cul3-RING ubiquitin ligase complex / positive regulation of intracellular estrogen receptor signaling pathway / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of mitophagy / Prolactin receptor signaling / p53-Dependent G1 DNA Damage Response / RSV-host interactions / Constitutive Signaling by AKT1 E17K in Cancer / PTK6 Regulates Cell Cycle / protein kinase inhibitor activity / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / inner ear development / cullin family protein binding / regulation of G1/S transition of mitotic cell cycle / negative regulation of vascular associated smooth muscle cell proliferation / protein K63-linked ubiquitination / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / protein monoubiquitination / ubiquitin ligase complex / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / ubiquitin-like ligase-substrate adaptor activity / Cajal body / protein K48-linked ubiquitination / Cyclin E associated events during G1/S transition / positive regulation of double-strand break repair via homologous recombination / Cyclin A:Cdk2-associated events at S phase entry / Nuclear events stimulated by ALK signaling in cancer / cyclin-dependent protein kinase holoenzyme complex / Notch signaling pathway / transcription-coupled nucleotide-excision repair / Maturation of protein E / Maturation of protein E / positive regulation of microtubule polymerization / 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 Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.91 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Horn-Ghetko, D. / Prabu, J.R. / Schulman, B.A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | Germany, 2items
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Citation | Journal: Nature / Year: 2021Title: 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 |
|
-
Structure visualization
| Movie |
Movie viewer |
|---|---|
| Structure viewer | Molecule: Molmil Jmol/JSmol |
-
Downloads & links
-
Download
| PDBx/mmCIF format | 7b5m.cif.gz | 308.2 KB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| PDB format | pdb7b5m.ent.gz | 234.8 KB | Display | PDB format |
| PDBx/mmJSON format | 7b5m.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 7b5m_validation.pdf.gz | 989.1 KB | Display | wwPDB validaton report |
|---|---|---|---|---|
| Full document | 7b5m_full_validation.pdf.gz | 1019.2 KB | Display | |
| Data in XML | 7b5m_validation.xml.gz | 60.6 KB | Display | |
| Data in CIF | 7b5m_validation.cif.gz | 90.6 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b5/7b5m ftp://data.pdbj.org/pub/pdb/validation_reports/b5/7b5m | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 12040MC ![]() 7b5lC ![]() 7b5nC ![]() 7b5rC ![]() 7b5sC C: citing same article ( M: map data used to model this data |
|---|---|
| Similar structure data |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
Components
-Protein , 2 types, 2 molecules CU
| #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 |
|---|---|
| #6: 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: ![]() |
-E3 ubiquitin-protein ligase ... , 2 types, 2 molecules HR
| #2: Protein | Mass: 64005.605 Da / Num. of mol.: 1 / Mutation: F430A, E431A, E503A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ARIH1, ARI, MOP6, UBCH7BP, HUSSY-27 / Production host: ![]() References: UniProt: Q9Y4X5, RBR-type E3 ubiquitin transferase |
|---|---|
| #7: 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 |
-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.) Homo sapiens (human) / Gene: SKP2, FBXL1 / Production host: ![]() |
|---|---|
| #5: Protein | Mass: 18679.965 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SKP1, EMC19, OCP2, SKP1A, TCEB1L / Production host: ![]() |
-Cyclin-dependent ... , 2 types, 2 molecules KP
| #4: Protein | Mass: 9679.211 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CKS1B, CKS1, PNAS-143, PNAS-16 / Production host: ![]() |
|---|---|
| #8: Protein | Mass: 22185.262 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDKN1B, KIP1 / Production host: synthetic construct (others) / References: UniProt: P46527 |
-Non-polymers , 1 types, 5 molecules 
| #9: Chemical | ChemComp-ZN / |
|---|
-Details
| Has ligand of interest | N |
|---|---|
| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component |
| ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Molecular weight | Value: 0.25 MDa | ||||||||||||||||||||||||||||||
| Source (natural) |
| ||||||||||||||||||||||||||||||
| Source (recombinant) |
| ||||||||||||||||||||||||||||||
| 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 |
|---|---|
| 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 | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.91 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 759489 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
|
Movie
Controller
About Yorodumi



Homo sapiens (human)
Germany, 2items
Citation

UCSF Chimera



















PDBj





























Trichoplusia ni (cabbage looper)

