+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34462 | |||||||||
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Title | Cryo-EM Structure of the KBTBD2-CRL3~N8(removed)-CSN complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | ligase / complex | |||||||||
Function / homology | Function and homology information regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion ...regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion / deNEDDylase activity / GTPase inhibitor activity / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / regulation of protein neddylation / protein deneddylation / eukaryotic translation initiation factor 3 complex / activation of NF-kappaB-inducing kinase activity / 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 / embryonic cleavage / cell projection organization / COP9 signalosome / 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 / regulation of JNK cascade / metal-dependent deubiquitinase activity / Hydrolases; Acting on peptide bonds (peptidases) / 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 / inner cell mass cell proliferation / 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 / stress fiber assembly / Prolactin receptor signaling / skeletal muscle cell differentiation / protein monoubiquitination / positive regulation of cytokinesis / cullin family protein binding / cyclin binding / ubiquitin-like ligase-substrate adaptor activity / response to light stimulus / 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 / JNK cascade / gastrulation / positive regulation of TORC1 signaling / T cell activation / translation initiation factor activity / phosphatidylinositol 3-kinase/protein kinase B signal transduction / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / cellular response to amino acid stimulus / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / lipid metabolic process / 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 / positive regulation of DNA-binding transcription factor activity / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.51 Å | |||||||||
Authors | Hu Y / Mao Q / Chen Z / Sun L | |||||||||
Funding support | China, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_34462.map.gz | 34.2 MB | EMDB map data format | |
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Header (meta data) | emd-34462-v30.xml emd-34462.xml | 31.1 KB 31.1 KB | Display Display | EMDB header |
Images | emd_34462.png | 99.3 KB | ||
Filedesc metadata | emd-34462.cif.gz | 9.1 KB | ||
Others | emd_34462_half_map_1.map.gz emd_34462_half_map_2.map.gz | 29.6 MB 29.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34462 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34462 | HTTPS FTP |
-Validation report
Summary document | emd_34462_validation.pdf.gz | 658 KB | Display | EMDB validaton report |
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Full document | emd_34462_full_validation.pdf.gz | 657.6 KB | Display | |
Data in XML | emd_34462_validation.xml.gz | 10.8 KB | Display | |
Data in CIF | emd_34462_validation.cif.gz | 12.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34462 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34462 | HTTPS FTP |
-Related structure data
Related structure data | 8h3aMC 8gq6C 8h33C 8h34C 8h35C 8h36C 8h37C 8h38C 8h3fC 8h3qC 8h3rC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_34462.map.gz / Format: CCP4 / Size: 38.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 2.088 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_34462_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_34462_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Cryo-EM Structure of the KBTBD2-CRL3~N8-CSN complex
+Supramolecule #1: Cryo-EM Structure of the KBTBD2-CRL3~N8-CSN complex
+Supramolecule #2: CSN
+Supramolecule #3: KBTBD2, Cullin-3, Rbx1
+Macromolecule #1: COP9 signalosome complex subunit 5
+Macromolecule #2: COP9 signalosome complex subunit 1
+Macromolecule #3: COP9 signalosome complex subunit 2
+Macromolecule #4: COP9 signalosome complex subunit 3
+Macromolecule #5: COP9 signalosome complex subunit 4
+Macromolecule #6: COP9 signalosome complex subunit 6
+Macromolecule #7: COP9 signalosome complex subunit 7b
+Macromolecule #8: COP9 signalosome complex subunit 8
+Macromolecule #9: Kelch repeat and BTB domain-containing protein 2
+Macromolecule #10: Cullin-3
+Macromolecule #11: E3 ubiquitin-protein ligase RBX1
+Macromolecule #12: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 53.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: Details: 6r7f |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 7.51 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 55391 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |