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Open data
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Basic information
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Title | local refinement of KBTBD2-CRL3-CSN(mutate) complex | |||||||||
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![]() | ligase / complex | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / Resolution: 4.25 Å | |||||||||
![]() | Hu Y / Mao Q / Chen Z / Sun L | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 29.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.5 KB 12.5 KB | Display Display | ![]() |
Images | ![]() | 74.7 KB | ||
Filedesc metadata | ![]() | 3.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8gq6C ![]() 8h33C ![]() 8h34C ![]() 8h35C ![]() 8h36C ![]() 8h37C ![]() 8h38C ![]() 8h3aC ![]() 8h3fC ![]() 8h3qC ![]() 8h3rC C: citing same article ( |
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Links
EMDB pages | ![]() ![]() |
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Map
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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
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Sample components
-Entire : KBTBD2-CRL3~N8 dimer assemble with CSN(mutate) monomer
Entire | Name: KBTBD2-CRL3~N8 dimer assemble with CSN(mutate) monomer |
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Components |
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-Supramolecule #1: KBTBD2-CRL3~N8 dimer assemble with CSN(mutate) monomer
Supramolecule | Name: KBTBD2-CRL3~N8 dimer assemble with CSN(mutate) monomer type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#12 |
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Source (natural) | Organism: ![]() |
-Supramolecule #2: CSN
Supramolecule | Name: CSN / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#8 |
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-Supramolecule #3: KBTBD2,CRL3
Supramolecule | Name: KBTBD2,CRL3 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #9-#11 |
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-Supramolecule #4: N8
Supramolecule | Name: N8 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #12 |
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-Experimental details
-Structure determination
![]() | single particle reconstruction |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.8 |
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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: ![]() |
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 |
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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: 4.25 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 146505 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |