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Open data
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Basic information
Entry | Database: PDB / ID: 8h38 | ||||||
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Title | Cryo-EM Structure of the KBTBD2-CRL3~N8-CSN(mutate) complex | ||||||
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![]() | LIGASE / complex | ||||||
Function / homology | ![]() 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 / regulation of proteolysis / positive regulation of protein autoubiquitination / protein neddylation / 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 / TGF-beta receptor signaling activates SMADs / cullin family protein binding / regulation of JNK cascade / ubiquitin-like ligase-substrate adaptor activity / response to light stimulus / sperm flagellum / anatomical structure morphogenesis / protein K48-linked ubiquitination / RHOBTB2 GTPase cycle / protein autoubiquitination / endoplasmic reticulum to Golgi vesicle-mediated transport / Nuclear events stimulated by ALK signaling in cancer / 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 cellular response to insulin stimulus / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / cyclin binding / post-translational protein modification / 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 / cellular response to amino acid stimulus / Iron uptake and transport / 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 Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 842.8 KB | Display | ![]() |
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PDB format | ![]() | 681.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 34455MC ![]() 8gq6C ![]() 8h33C ![]() 8h34C ![]() 8h35C ![]() 8h36C ![]() 8h37C ![]() 8h3aC ![]() 8h3fC ![]() 8h3qC ![]() 8h3rC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-COP9 signalosome complex subunit ... , 8 types, 8 molecules ABCDEFGH
#1: Protein | Mass: 59122.176 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 51664.570 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Protein | Mass: 47924.008 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#4: Protein | Mass: 46322.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#5: Protein | Mass: 37554.672 Da / Num. of mol.: 1 / Mutation: H138A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: Q92905, Hydrolases; Acting on peptide bonds (peptidases) |
#6: Protein | Mass: 36203.398 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#7: Protein | Mass: 29656.928 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#8: Protein | Mass: 23245.543 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein , 4 types, 5 molecules IMLRN
#9: Protein | Mass: 71403.367 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #10: Protein | | Mass: 89063.328 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #11: Protein | | Mass: 12289.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase #12: Protein | | Mass: 8573.978 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 1 types, 4 molecules ![](data/chem/img/ZN.gif)
#13: Chemical | ChemComp-ZN / |
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-Details
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 |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||||||||||||||
Source (recombinant) |
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Buffer solution | pH: 7.8 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: NO |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 53 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||
3D reconstruction | Resolution: 4.25 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 146505 / Symmetry type: POINT |