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Yorodumi- PDB-8je2: Cryo-EM structure of neddylated Cul2-Rbx1-EloBC-FEM1B complexed w... -
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-Basic information
Entry | Database: PDB / ID: 8je2 | ||||||
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Title | Cryo-EM structure of neddylated Cul2-Rbx1-EloBC-FEM1B complexed with FNIP1-FLCN | ||||||
Components |
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Keywords | LIGASE / Complex / E3 ubiquitin ligase / Cullin | ||||||
Function / homology | Function and homology information regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / positive regulation of B cell apoptotic process / negative regulation of lysosome organization / regulation of pro-B cell differentiation / branching involved in prostate gland morphogenesis / immature B cell differentiation / ATPase inhibitor activity / Amino acids regulate mTORC1 / regulation of DNA damage checkpoint ...regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / positive regulation of B cell apoptotic process / negative regulation of lysosome organization / regulation of pro-B cell differentiation / branching involved in prostate gland morphogenesis / immature B cell differentiation / ATPase inhibitor activity / Amino acids regulate mTORC1 / regulation of DNA damage checkpoint / B cell apoptotic process / negative regulation of TOR signaling / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / target-directed miRNA degradation / elongin complex / VCB complex / death receptor binding / regulation of extrinsic apoptotic signaling pathway via death domain receptors / Cul5-RING ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul2-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / TOR signaling / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / enzyme activator activity / positive regulation of TOR signaling / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / positive regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / cellular response to starvation / intrinsic apoptotic signaling pathway / B cell differentiation / transcription corepressor binding / transcription elongation by RNA polymerase II / transcription initiation at RNA polymerase II promoter / positive regulation of protein-containing complex assembly / TP53 Regulates Transcription of DNA Repair Genes / regulation of protein phosphorylation / Vif-mediated degradation of APOBEC3G / G1/S transition of mitotic cell cycle / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / Regulation of expression of SLITs and ROBOs / ubiquitin-protein transferase activity / protein-macromolecule adaptor activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of peptidyl-serine phosphorylation / Neddylation / ubiquitin-dependent protein catabolic process / protein-folding chaperone binding / proteasome-mediated ubiquitin-dependent protein catabolic process / protein-containing complex assembly / protein ubiquitination / positive regulation of protein phosphorylation / lysosomal membrane / negative regulation of cell population proliferation / apoptotic process / ubiquitin protein ligase binding / protein-containing complex binding / nucleolus / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / enzyme binding / nucleoplasm / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.63 Å | ||||||
Authors | Dai, Z. / Liang, L. / Yin, Y.X. | ||||||
Funding support | China, 1items
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Citation | Journal: EMBO J / Year: 2024 Title: Structural insights into the ubiquitylation strategy of the oligomeric CRL2 E3 ubiquitin ligase. Authors: Zonglin Dai / Ling Liang / Weize Wang / Peng Zuo / Shang Yu / Yaqi Liu / Xuyang Zhao / Yishuo Lu / Yan Jin / Fangting Zhang / Dian Ding / Weiwei Deng / Yuxin Yin / Abstract: Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been ...Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2 in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2 is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2 according to substrates with different scales. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8je2.cif.gz | 289.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8je2.ent.gz | 201 KB | Display | PDB format |
PDBx/mmJSON format | 8je2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/je/8je2 ftp://data.pdbj.org/pub/pdb/validation_reports/je/8je2 | HTTPS FTP |
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-Related structure data
Related structure data | 36183MC 8ij1C 8je1C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 5 types, 5 molecules ABCDH
#1: Protein | Mass: 87927.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q13617 |
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#2: Protein | Mass: 11748.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15370 |
#3: Protein | Mass: 11045.694 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15369 |
#4: Protein | Mass: 70688.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FEM1B, F1AA, KIAA0396 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UK73 |
#5: Protein | Mass: 131499.906 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FNIP1, KIAA1961 / Production host: Homo sapiens (human) / References: UniProt: Q8TF40 |
-Non-polymers , 1 types, 1 molecules
#6: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | Y |
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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 | Name: Neddylated Cul2-Rbx1-EloBC-FEM1B complexed with FNIP1-FLCN Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1.93 mg/ml / 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 FIELDBright-field microscopy / Nominal defocus max: 2000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 433719 / Symmetry type: POINT |