+Open data
-Basic information
Entry | Database: PDB / ID: 8khp | ||||||
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Title | CULLIN3-KLHL22-RBX1 E3 ligase | ||||||
Components |
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Keywords | STRUCTURAL PROTEIN / E3 ligase | ||||||
Function / homology | Function and homology information liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division ...liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / RHOBTB3 ATPase cycle / cullin-RING ubiquitin ligase complex / cellular response to L-leucine / embryonic cleavage / cell projection organization / Cul7-RING ubiquitin ligase complex / positive regulation of mitotic metaphase/anaphase transition / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / Notch binding / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / RHOBTB1 GTPase cycle / fibroblast apoptotic process / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / negative regulation of Rho protein signal transduction / 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 / mitotic metaphase chromosome alignment / Cul3-RING ubiquitin ligase complex / intercellular bridge / mitotic spindle assembly checkpoint signaling / stress fiber assembly / Prolactin receptor signaling / protein monoubiquitination / positive regulation of cytokinesis / mitotic sister chromatid segregation / cullin family protein binding / cyclin binding / ubiquitin-like ligase-substrate adaptor activity / sperm flagellum / protein K48-linked ubiquitination / RHOBTB2 GTPase cycle / protein autoubiquitination / endoplasmic reticulum to Golgi vesicle-mediated transport / post-translational protein modification / Nuclear events stimulated by ALK signaling in cancer / regulation of cellular response to insulin stimulus / gastrulation / 14-3-3 protein binding / positive regulation of TORC1 signaling / T cell activation / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / negative regulation of autophagy / cellular response to amino acid stimulus / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / 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 / Orc1 removal from chromatin / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / protein destabilization / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / G1/S transition of mitotic cell cycle / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / mitotic spindle / Wnt signaling pathway / spindle pole / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of expression of SLITs and ROBOs / Formation of Incision Complex in GG-NER / Dual incision in TC-NER Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.67 Å | ||||||
Authors | Su, M.-Y. / Su, M.-Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Structure / Year: 2023 Title: Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme. Authors: Fei Teng / Yang Wang / Ming Liu / Shuyun Tian / Goran Stjepanovic / Ming-Yuan Su / Abstract: CULLIN-RING ligases constitute the largest group of E3 ubiquitin ligases. While some CULLIN family members recruit adapters before engaging further with different substrate receptors, homo-dimeric ...CULLIN-RING ligases constitute the largest group of E3 ubiquitin ligases. While some CULLIN family members recruit adapters before engaging further with different substrate receptors, homo-dimeric BTB-Kelch family proteins combine adapter and substrate receptor into a single polypeptide for the CULLIN3 family. However, the entire structural assembly and molecular details have not been elucidated to date. Here, we present a cryo-EM structure of the CULLIN3 in complex with Kelch-like protein 22 (KLHL22) and a mitochondrial glutamate dehydrogenase complex I (GDH1) at 3.06 Å resolution. The structure adopts a W-shaped architecture formed by E3 ligase dimers. Three CULLIN3 dimers were found to be dynamically associated with a single GDH1 hexamer. CULLIN3 ligase mediated the polyubiquitination of GDH1 in vitro. Together, these results enabled the establishment of a structural model for understanding the complete assembly of BTB-Kelch proteins with CULLIN3 and how together they recognize oligomeric substrates and target them for ubiquitination. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8khp.cif.gz | 411 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8khp.ent.gz | 305.2 KB | Display | PDB format |
PDBx/mmJSON format | 8khp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8khp_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8khp_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8khp_validation.xml.gz | 70.4 KB | Display | |
Data in CIF | 8khp_validation.cif.gz | 112.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kh/8khp ftp://data.pdbj.org/pub/pdb/validation_reports/kh/8khp | HTTPS FTP |
-Related structure data
Related structure data | 37247MC 8kgyC 8w4jC C: citing same article (ref.) M: map data used to model this data |
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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
#1: Protein | Mass: 71744.594 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KLHL22 / Production host: Homo sapiens (human) / References: UniProt: Q53GT1 #2: Protein | Mass: 89063.328 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL3, KIAA0617 / Production host: Homo sapiens (human) / References: UniProt: Q13618 #3: Protein | Mass: 12289.977 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: Homo sapiens (human) References: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase |
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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: CULLIN3-KLHL22-RBX1 E3 ligase / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1900 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 1.07 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.67 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 181834 / Symmetry type: POINT | ||||||||||||||||||||||||
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