+Open data
-Basic information
Entry | Database: PDB / ID: 8kbz | |||||||||
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Title | Cryo-EM structure of human ATG9A in LMNG micelles | |||||||||
Components | Autophagy-related protein 9A | |||||||||
Keywords | MEMBRANE PROTEIN / Lipid scramblase / ATG9A / single particle cryo-EM | |||||||||
Function / homology | Function and homology information phospholipid scramblase activity / programmed necrotic cell death / protein localization to phagophore assembly site / phagophore assembly site membrane / piecemeal microautophagy of the nucleus / phagophore assembly site / bone morphogenesis / autophagy of mitochondrion / reticulophagy / Macroautophagy ...phospholipid scramblase activity / programmed necrotic cell death / protein localization to phagophore assembly site / phagophore assembly site membrane / piecemeal microautophagy of the nucleus / phagophore assembly site / bone morphogenesis / autophagy of mitochondrion / reticulophagy / Macroautophagy / autophagosome assembly / autophagosome / PINK1-PRKN Mediated Mitophagy / mitochondrial membrane / trans-Golgi network / recycling endosome / recycling endosome membrane / late endosome / late endosome membrane / endosome / Golgi membrane / intracellular membrane-bounded organelle / endoplasmic reticulum membrane / Golgi apparatus / mitochondrion / membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.97 Å | |||||||||
Authors | Yang, W. / Goran, S. | |||||||||
Funding support | China, 2items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Structural basis for lipid transfer by the ATG2A-ATG9A complex. Authors: Yang Wang / Selma Dahmane / Rujuan Ti / Xinyi Mai / Lizhe Zhu / Lars-Anders Carlson / Goran Stjepanovic / Abstract: Autophagy is characterized by the formation of double-membrane vesicles called autophagosomes. Autophagy-related proteins (ATGs) 2A and 9A have an essential role in autophagy by mediating lipid ...Autophagy is characterized by the formation of double-membrane vesicles called autophagosomes. Autophagy-related proteins (ATGs) 2A and 9A have an essential role in autophagy by mediating lipid transfer and re-equilibration between membranes for autophagosome formation. Here we report the cryo-electron microscopy structures of human ATG2A in complex with WD-repeat protein interacting with phosphoinositides 4 (WIPI4) at 3.2 Å and the ATG2A-WIPI4-ATG9A complex at 7 Å global resolution. On the basis of molecular dynamics simulations, we propose a mechanism of lipid extraction from the donor membranes. Our analysis revealed 3:1 stoichiometry of the ATG9A-ATG2A complex, directly aligning the ATG9A lateral pore with ATG2A lipid transfer cavity, and an interaction of the ATG9A trimer with both the N-terminal and the C-terminal tip of rod-shaped ATG2A. Cryo-electron tomography of ATG2A liposome-binding states showed that ATG2A tethers lipid vesicles at different orientations. In summary, this study provides a molecular basis for the growth of the phagophore membrane and lends structural insights into spatially coupled lipid transport and re-equilibration during autophagosome formation. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8kbz.cif.gz | 244.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8kbz.ent.gz | 172.8 KB | Display | PDB format |
PDBx/mmJSON format | 8kbz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8kbz_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 8kbz_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 8kbz_validation.xml.gz | 63.2 KB | Display | |
Data in CIF | 8kbz_validation.cif.gz | 94.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kb/8kbz ftp://data.pdbj.org/pub/pdb/validation_reports/kb/8kbz | HTTPS FTP |
-Related structure data
Related structure data | 37088MC 8kbxC 8kbyC 8kc3C 8y1lC 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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-Components
#1: Protein | Mass: 94551.031 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ATG9A, APG9L1 / Production host: Homo sapiens (human) / References: UniProt: Q7Z3C6 |
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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: ATG9A trimer / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.283 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
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 magnification: 105000 X / Nominal defocus max: 1900 nm / Nominal defocus min: 1400 nm / C2 aperture diameter: 100 µm |
Image recording | Electron dose: 65.17 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.97 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 224219 / Symmetry type: POINT |