+Open data
-Basic information
Entry | Database: PDB / ID: 8h34 | ||||||
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Title | Cryo-EM Structure of the KBTBD2-Cul3-Rbx1 hexameric complex | ||||||
Components |
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Keywords | LIGASE / complex | ||||||
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 / COPII vesicle coating / anaphase-promoting complex-dependent catabolic process / 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 / COPII vesicle coating / anaphase-promoting complex-dependent catabolic process / stem cell division / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / RHOBTB3 ATPase cycle / embryonic cleavage / cell projection organization / positive regulation of mitotic metaphase/anaphase transition / 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 / positive regulation of protein autoubiquitination / protein neddylation / fibroblast apoptotic process / Notch binding / NEDD8 ligase activity / RHOBTB1 GTPase cycle / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / negative regulation of Rho protein signal transduction / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / mitotic metaphase chromosome alignment / 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 / stress fiber assembly / positive regulation of cytokinesis / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / sperm flagellum / endoplasmic reticulum to Golgi vesicle-mediated transport / RHOBTB2 GTPase cycle / protein autoubiquitination / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / gastrulation / positive regulation of TORC1 signaling / intrinsic apoptotic signaling pathway / post-translational protein modification / phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of cellular response to insulin stimulus / cyclin binding / Regulation of BACH1 activity / T cell activation / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / cellular response to amino acid stimulus / 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 / protein destabilization / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / response to insulin / 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 / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / lipid metabolic process / 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 / mitotic spindle / Wnt signaling pathway / NOTCH1 Intracellular Domain Regulates Transcription / Regulation of expression of SLITs and ROBOs / spindle pole / 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 Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 7.99 Å | ||||||
Authors | Hu, Y. / Mao, Q. / Chen, Z. / Sun, L. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3. Authors: Yuxia Hu / Zhao Zhang / Qiyu Mao / Xiang Zhang / Aihua Hao / Yu Xun / Yeda Wang / Lin Han / Wuqiang Zhan / Qianying Liu / Yue Yin / Chao Peng / Eva Marie Y Moresco / Zhenguo Chen / Bruce Beutler / Lei Sun / Abstract: Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. ...Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. Cellular levels of the regulatory p85α subunit are tightly controlled by regulated proteasomal degradation. In adipose tissue and growth plates, failure of K48-linked p85α ubiquitination causes diabetes, lipodystrophy and dwarfism in mice, as in humans with SHORT syndrome. Here we elucidated the structures of the key ubiquitin ligase complexes regulating p85α availability. Specificity is provided by the substrate receptor KBTBD2, which recruits p85α to the cullin3-RING E3 ubiquitin ligase (CRL3). CRL3 forms multimers, which disassemble into dimers upon substrate binding (CRL3-p85α) and/or neddylation by the activator NEDD8 (CRL3~N8), leading to p85α ubiquitination and degradation. Deactivation involves dissociation of NEDD8 mediated by the COP9 signalosome and displacement of KBTBD2 by the inhibitor CAND1. The hereby identified structural basis of p85α regulation opens the way to better understanding disturbances of glucose regulation, growth and cancer. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8h34.cif.gz | 1.4 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8h34.ent.gz | 1.2 MB | Display | PDB format |
PDBx/mmJSON format | 8h34.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8h34_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8h34_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 8h34_validation.xml.gz | 200.3 KB | Display | |
Data in CIF | 8h34_validation.cif.gz | 313.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h3/8h34 ftp://data.pdbj.org/pub/pdb/validation_reports/h3/8h34 | HTTPS FTP |
-Related structure data
Related structure data | 34450MC 8gq6C 8h33C 8h35C 8h36C 8h37C 8h38C 8h3aC 8h3fC 8h3qC 8h3rC 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
#1: Protein | Mass: 89063.328 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL3, KIAA0617 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q13618 #2: Protein | Mass: 71403.367 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8IY47 #3: Protein | Mass: 13970.756 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1, RNF75, ROC1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase #4: Chemical | ChemComp-ZN / 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: KBTBD2-Cul3-Rbx1 hexameric complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
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 |
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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 FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 45 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Resolution: 7.99 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 51689 / Symmetry type: POINT |