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Open data
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Basic information
Entry | Database: PDB / ID: 8d9x | ||||||
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Title | Cryo-EM structure of human DELE1 in oligomeric form | ||||||
![]() | Maltodextrin-binding protein,DAP3-binding cell death enhancer 1 short form | ||||||
![]() | PROTEIN BINDING / Oligomer / Mitochondria / Integrated Stress Response / Kinase / Tetratricopeptide repeat | ||||||
Function / homology | ![]() regulation of cysteine-type endopeptidase activity involved in apoptotic process / integrated stress response signaling / HRI-mediated signaling / carbohydrate transmembrane transporter activity / extrinsic apoptotic signaling pathway via death domain receptors / protein serine/threonine kinase activator activity / outer membrane-bounded periplasmic space / mitochondrial inner membrane / protein kinase binding / mitochondrion / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||
![]() | Yang, J. / Lander, G.C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: DELE1 oligomerization promotes integrated stress response activation. Authors: Jie Yang / Kelsey R Baron / Daniel E Pride / Anette Schneemann / Xiaoyan Guo / Wenqian Chen / Albert S Song / Giovanni Aviles / Martin Kampmann / R Luke Wiseman / Gabriel C Lander / ![]() Abstract: Mitochondria are dynamic organelles that continually respond to cellular stress. Recent studies have demonstrated that mitochondrial stress is relayed from mitochondria to the cytosol by the release ...Mitochondria are dynamic organelles that continually respond to cellular stress. Recent studies have demonstrated that mitochondrial stress is relayed from mitochondria to the cytosol by the release of a proteolytic fragment of DELE1 that binds to the eIF2α kinase HRI to initiate integrated stress response (ISR) signaling. We report the cryo-electron microscopy structure of the C-terminal cleavage product of human DELE1, which assembles into a high-order oligomer. The oligomer consists of eight DELE1 monomers that assemble with D symmetry via two sets of hydrophobic inter-subunit interactions. We identified the key residues involved in DELE1 oligomerization, and confirmed their role in stabilizing the octamer in vitro and in cells using mutagenesis. We further show that assembly-impaired DELE1 mutants are compromised in their ability to induce HRI-dependent ISR activation in cell culture models. Together, our findings provide molecular insights into the activity of DELE1 and how it signals to promote ISR activity following mitochondrial insult. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 330.2 KB | Display | ![]() |
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PDB format | ![]() | 244.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27269MC 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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Components
#1: Protein | Mass: 73343.836 Da / Num. of mol.: 8 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: malE, GUB92_19955, NCTC8450_00456, NCTC9775_03059, DELE1, DELE, KIAA0141 Production host: ![]() ![]() References: UniProt: A0A376KDN7, UniProt: Q14154 |
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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
Component | Name: Oligomeric structure of human DELE1 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 3600 X / Calibrated magnification: 43478 X / Nominal defocus max: 1300 nm / Nominal defocus min: 700 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
Symmetry | Point symmetry: D4 (2x4 fold dihedral) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 92455 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||
Refine LS restraints |
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