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Yorodumi- PDB-8qbn: Structure of the non-canonical CTLH E3 substrate receptor WDR26 b... -
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-Basic information
Entry | Database: PDB / ID: 8qbn | ||||||||||||
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Title | Structure of the non-canonical CTLH E3 substrate receptor WDR26 bound to YPEL5 | ||||||||||||
Components |
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Keywords | LIGASE / E3 ubiquitin ligase / CTLH / GID / NMNAT1 / YPEL5 | ||||||||||||
Function / homology | Function and homology information GID complex / mitotic spindle pole / ubiquitin ligase complex / tertiary granule lumen / midbody / proteasome-mediated ubiquitin-dependent protein catabolic process / ficolin-1-rich granule lumen / cell population proliferation / centrosome / Neutrophil degranulation ...GID complex / mitotic spindle pole / ubiquitin ligase complex / tertiary granule lumen / midbody / proteasome-mediated ubiquitin-dependent protein catabolic process / ficolin-1-rich granule lumen / cell population proliferation / centrosome / Neutrophil degranulation / mitochondrion / extracellular region / nucleoplasm / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||
Authors | Chrustowicz, J. / Sherpa, D. / Schulman, B.A. | ||||||||||||
Funding support | Germany, European Union, 3items
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Citation | Journal: Mol Cell / Year: 2024 Title: Non-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism. Authors: Karthik V Gottemukkala / Jakub Chrustowicz / Dawafuti Sherpa / Sara Sepic / Duc Tung Vu / Özge Karayel / Eleftheria C Papadopoulou / Annette Gross / Kenji Schorpp / Susanne von Gronau / ...Authors: Karthik V Gottemukkala / Jakub Chrustowicz / Dawafuti Sherpa / Sara Sepic / Duc Tung Vu / Özge Karayel / Eleftheria C Papadopoulou / Annette Gross / Kenji Schorpp / Susanne von Gronau / Kamyar Hadian / Peter J Murray / Matthias Mann / Brenda A Schulman / Arno F Alpi / Abstract: The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of metabolic ...The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of metabolic enzyme substrates. The orthologous higher eukaryotic C-terminal to LisH (CTLH) E3 complex has been proposed to also recognize substrates through an alternative subunit, WDR26, which promotes the formation of supramolecular CTLH E3 assemblies. Here, we discover that human WDR26 binds the metabolic enzyme nicotinamide/nicotinic-acid-mononucleotide-adenylyltransferase 1 (NMNAT1) and mediates its CTLH E3-dependent ubiquitylation independently of canonical GID/CTLH E3-family substrate receptors. The CTLH subunit YPEL5 inhibits NMNAT1 ubiquitylation and cellular turnover by WDR26-CTLH E3, thereby affecting NMNAT1-mediated metabolic activation and cytotoxicity of the prodrug tiazofurin. Cryoelectron microscopy (cryo-EM) structures of NMNAT1- and YPEL5-bound WDR26-CTLH E3 complexes reveal an internal basic degron motif of NMNAT1 essential for targeting by WDR26-CTLH E3 and degron mimicry by YPEL5's N terminus antagonizing substrate binding. Thus, our data provide a mechanistic understanding of how YPEL5-WDR26-CTLH E3 acts as a modulator of NMNAT1-dependent metabolism. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8qbn.cif.gz | 172.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8qbn.ent.gz | 130.7 KB | Display | PDB format |
PDBx/mmJSON format | 8qbn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8qbn_validation.pdf.gz | 939.1 KB | Display | wwPDB validaton report |
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Full document | 8qbn_full_validation.pdf.gz | 942.8 KB | Display | |
Data in XML | 8qbn_validation.xml.gz | 38.7 KB | Display | |
Data in CIF | 8qbn_validation.cif.gz | 57.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qb/8qbn ftp://data.pdbj.org/pub/pdb/validation_reports/qb/8qbn | HTTPS FTP |
-Related structure data
Related structure data | 18316MC 8qe8C C: citing same article (ref.) M: map data used to model this data |
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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: 70539.773 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WDR26, CDW2, MIP2, PRO0852 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9H7D7 #2: Protein | | Mass: 13860.658 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: YPEL5, CGI-127 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62699 #3: Chemical | 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: Complex of human WDR26-CTLH E3 ligase bound to YPEL5 / Type: COMPLEX Details: Map obtained by focused refinement over YPEL5-bound WDR26 dimer Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.9 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Sample mixed with 0.01% beta-OG right before plunging |
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: 2300 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 71.2 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 77172 / Symmetry type: POINT | ||||||||||||||||||||||||
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