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Yorodumi- PDB-8h37: Cryo-EM Structure of the KBTBD2-CUL3-Rbx1-p85a tetrameric complex -
+Open data
-Basic information
Entry | Database: PDB / ID: 8h37 | ||||||
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Title | Cryo-EM Structure of the KBTBD2-CUL3-Rbx1-p85a tetrameric 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 / perinuclear endoplasmic reticulum membrane / polar microtubule / regulation of toll-like receptor 4 signaling pathway / phosphatidylinositol kinase activity ...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 / perinuclear endoplasmic reticulum membrane / polar microtubule / regulation of toll-like receptor 4 signaling pathway / phosphatidylinositol kinase activity / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division / phosphatidylinositol 3-kinase regulator activity / IRS-mediated signalling / cullin-RING-type E3 NEDD8 transferase / positive regulation of focal adhesion disassembly / phosphatidylinositol 3-kinase activator activity / cellular response to chemical stress / NEDD8 transferase activity / RHOBTB3 ATPase cycle / interleukin-18-mediated signaling pathway / cullin-RING ubiquitin ligase complex / PI3K events in ERBB4 signaling / myeloid leukocyte migration / embryonic cleavage / 1-phosphatidylinositol-3-kinase regulator activity / cell projection organization / Cul7-RING ubiquitin ligase complex / positive regulation of mitotic metaphase/anaphase transition / phosphatidylinositol 3-kinase regulatory subunit binding / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / Activated NTRK3 signals through PI3K / cis-Golgi network / ErbB-3 class receptor binding / kinase activator activity / positive regulation of protein autoubiquitination / transmembrane receptor protein tyrosine kinase adaptor activity / RHOF GTPase cycle / RHOD GTPase cycle / protein neddylation / Signaling by cytosolic FGFR1 fusion mutants / positive regulation of endoplasmic reticulum unfolded protein response / phosphatidylinositol 3-kinase complex, class IA / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase complex / Nephrin family interactions / Signaling by LTK in cancer / NEDD8 ligase activity / Notch binding / RND1 GTPase cycle / Cul5-RING ubiquitin ligase complex / Costimulation by the CD28 family / Signaling by LTK / negative regulation of response to oxidative stress / RHOBTB1 GTPase cycle / positive regulation of leukocyte migration / MET activates PI3K/AKT signaling / RND2 GTPase cycle / fibroblast apoptotic process / PI3K/AKT activation / positive regulation of filopodium assembly / RND3 GTPase cycle / negative regulation of stress fiber assembly / growth hormone receptor signaling pathway / 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 / natural killer cell mediated cytotoxicity / insulin binding / 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 / RHOV GTPase cycle / mitotic metaphase chromosome alignment / Cul3-RING ubiquitin ligase complex / Signaling by ALK / negative regulation of cell-matrix adhesion / RHOB GTPase cycle / GP1b-IX-V activation signalling / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / stress fiber assembly / PI-3K cascade:FGFR2 / Prolactin receptor signaling / PI-3K cascade:FGFR4 / RHOC GTPase cycle / RHOJ GTPase cycle / PI-3K cascade:FGFR1 / negative regulation of osteoclast differentiation / protein monoubiquitination / positive regulation of cytokinesis / intracellular glucose homeostasis / cullin family protein binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 7.52 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 | 8h37.cif.gz | 1.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8h37.ent.gz | 897.1 KB | Display | PDB format |
PDBx/mmJSON format | 8h37.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h3/8h37 ftp://data.pdbj.org/pub/pdb/validation_reports/h3/8h37 | HTTPS FTP |
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-Related structure data
Related structure data | 34453MC 8gq6C 8h33C 8h34C 8h35C 8h36C 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.: 4 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: 12289.977 Da / Num. of mol.: 4 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 #3: Protein | Mass: 71431.375 Da / Num. of mol.: 4 / Mutation: S252D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KBTBD2, BKLHD1, KIAA1489, CGI-73 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8IY47 #4: Protein | Mass: 83710.281 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3R1, GRB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P27986 #5: 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-p85a tetrameric complex / Type: COMPLEX / Entity ID: #1-#4 / 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: 8.5 |
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: 7.52 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 239068 / Symmetry type: POINT |