[English] 日本語
Yorodumi- PDB-8wqe: Cryo-EM structure of CUL2-RBX1-ELOB-ELOC-FEM1B bound with the C-d... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8wqe | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of CUL2-RBX1-ELOB-ELOC-FEM1B bound with the C-degron of CUX1 (conformation 1) | ||||||
Components |
| ||||||
Keywords | LIGASE / E3 ubiquitin ligase / Pro/C-degron | ||||||
Function / homology | Function and homology information regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / Intra-Golgi traffic / branching involved in prostate gland morphogenesis / cullin-RING-type E3 NEDD8 transferase / intra-Golgi vesicle-mediated transport / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint ...regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / Intra-Golgi traffic / branching involved in prostate gland morphogenesis / cullin-RING-type E3 NEDD8 transferase / intra-Golgi vesicle-mediated transport / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / target-directed miRNA degradation / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / elongin complex / VCB complex / positive regulation of protein autoubiquitination / regulation of extrinsic apoptotic signaling pathway via death domain receptors / death receptor binding / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4B-RING E3 ubiquitin ligase complex / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / cullin family protein binding / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / 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 / protein K48-linked ubiquitination / RNA Polymerase II Transcription Elongation / Nuclear events stimulated by ALK signaling in cancer / Formation of RNA Pol II elongation complex / RNA Polymerase II Pre-transcription Events / positive regulation of TORC1 signaling / intrinsic apoptotic signaling pathway / post-translational protein modification / regulation of cellular response to insulin stimulus / Regulation of BACH1 activity / transcription corepressor binding / T cell activation / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / Degradation of DVL / cellular response to amino acid stimulus / transcription elongation by RNA polymerase II / Degradation of GLI1 by the proteasome / Recognition of DNA damage by PCNA-containing replication complex / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Inactivation of CSF3 (G-CSF) signaling / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Regulation of expression of SLITs and ROBOs / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Formation of Incision Complex in GG-NER / Interleukin-1 signaling / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Orc1 removal from chromatin / protein polyubiquitination / Regulation of RAS by GAPs / ubiquitin-protein transferase activity / positive regulation of protein catabolic process / G1/S transition of mitotic cell cycle / Regulation of RUNX2 expression and activity / cellular response to UV / MAPK cascade / ubiquitin protein ligase activity / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.38 Å | ||||||
Authors | Chen, X. / Zhang, K. / Xu, C. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2024 Title: Mechanism of Ψ-Pro/C-degron recognition by the CRL2 ubiquitin ligase. Authors: Xinyan Chen / Anat Raiff / Shanshan Li / Qiong Guo / Jiahai Zhang / Hualin Zhou / Richard T Timms / Xuebiao Yao / Stephen J Elledge / Itay Koren / Kaiming Zhang / Chao Xu / Abstract: The E3 ligase-degron interaction determines the specificity of the ubiquitin‒proteasome system. We recently discovered that FEM1B, a substrate receptor of Cullin 2-RING ligase (CRL2), recognizes C- ...The E3 ligase-degron interaction determines the specificity of the ubiquitin‒proteasome system. We recently discovered that FEM1B, a substrate receptor of Cullin 2-RING ligase (CRL2), recognizes C-degrons containing a C-terminal proline. By solving several cryo-EM structures of CRL2 bound to different C-degrons, we elucidate the dimeric assembly of the complex. Furthermore, we reveal distinct dimerization states of unmodified and neddylated CRL2 to uncover the NEDD8-mediated activation mechanism of CRL2. Our research also indicates that, FEM1B utilizes a bipartite mechanism to recognize both the C-terminal proline and an upstream aromatic residue within the substrate. These structural findings, complemented by in vitro ubiquitination and in vivo cell-based assays, demonstrate that CRL2-mediated polyubiquitination and subsequent protein turnover depend on both FEM1B-degron interactions and the dimerization state of the E3 ligase complex. Overall, this study deepens our molecular understanding of how Cullin-RING E3 ligase substrate selection mediates protein turnover. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8wqe.cif.gz | 635.4 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8wqe.ent.gz | 501.2 KB | Display | PDB format |
PDBx/mmJSON format | 8wqe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8wqe_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8wqe_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8wqe_validation.xml.gz | 95.6 KB | Display | |
Data in CIF | 8wqe_validation.cif.gz | 143.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wq/8wqe ftp://data.pdbj.org/pub/pdb/validation_reports/wq/8wqe | HTTPS FTP |
-Related structure data
Related structure data | 37742MC 8wqaC 8wqbC 8wqcC 8wqdC 8wqfC 8wqgC 8wqhC 8wqiC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Protein , 5 types, 10 molecules CADBEGFHJI
#1: Protein | Mass: 87114.750 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q13617 #2: Protein | Mass: 70355.062 Da / Num. of mol.: 2 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 #3: Protein | Mass: 10843.420 Da / Num. of mol.: 2 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: 13147.781 Da / Num. of mol.: 2 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 #5: Protein | Mass: 11196.830 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1, RNF75, ROC1 / Production host: Escherichia coli (E. coli) / References: UniProt: P62877 |
---|
-Protein/peptide / Non-polymers , 2 types, 8 molecules KL
#6: Protein/peptide | Mass: 3143.281 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUX1, CUTL1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q13948 #7: Chemical | ChemComp-ZN / |
---|
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cryo-EM structure of CUL2-RBX1-ELOB-ELOC-FEM1B bound with the C-degron of CUX1 (conformation 1) Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-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 / Nominal defocus max: 2900 nm / Nominal defocus min: 1500 nm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 57.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of real images: 8112 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
EM software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.38 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 252311 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|