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Yorodumi- EMDB-48233: PI3KC3-C1 bound to RAB1A. Local refinement of Bara like domains o... -
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Open data
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Basic information
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| Title | PI3KC3-C1 bound to RAB1A. Local refinement of Bara like domains of BECN1 and ATG14, and VPS15 WD40 domain | |||||||||
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Keywords | Complex / GTPase / GTP-binding / Autophagy / Kinase / Lipid Kinase / SIGNALING PROTEIN | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.62 Å | |||||||||
Authors | Cook ASI / Chen M / Hurley JH | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Science / Year: 2025Title: Structural pathway for PI3-kinase regulation by VPS15 in autophagy. Authors: Annan S I Cook / Minghao Chen / Thanh N Nguyen / Ainara Claveras Cabezudo / Grace Khuu / Shanlin Rao / Samantha N Garcia / Mingxuan Yang / Anthony T Iavarone / Xuefeng Ren / Michael Lazarou ...Authors: Annan S I Cook / Minghao Chen / Thanh N Nguyen / Ainara Claveras Cabezudo / Grace Khuu / Shanlin Rao / Samantha N Garcia / Mingxuan Yang / Anthony T Iavarone / Xuefeng Ren / Michael Lazarou / Gerhard Hummer / James H Hurley / ![]() Abstract: The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway ...The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway of enzyme activation through cryo-electron microscopy analysis of PI3KC3-C1. The inactive conformation of the VPS15 pseudokinase stabilizes the inactive conformation, sequestering its -myristate in the N-lobe of the pseudokinase. Upon activation, the myristate is liberated such that the VPS34 lipid kinase catalyzes phosphatidylinositol-3 phosphate production on membranes. The VPS15 pseudokinase domain binds tightly to guanosine triphosphate and stabilizes a web of interactions to autoinhibit the cytosolic complex and promote activation upon membrane binding. These findings show in atomistic detail how the VPS34 lipid kinase is activated in the context of a complete PI3K complex. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_48233.map.gz | 230.1 MB | EMDB map data format | |
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| Header (meta data) | emd-48233-v30.xml emd-48233.xml | 15.6 KB 15.6 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_48233_fsc.xml | 13.1 KB | Display | FSC data file |
| Images | emd_48233.png | 50.9 KB | ||
| Masks | emd_48233_msk_1.map | 244.1 MB | Mask map | |
| Filedesc metadata | emd-48233.cif.gz | 4.5 KB | ||
| Others | emd_48233_half_map_1.map.gz emd_48233_half_map_2.map.gz | 226.5 MB 226.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-48233 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-48233 | HTTPS FTP |
-Validation report
| Summary document | emd_48233_validation.pdf.gz | 948.9 KB | Display | EMDB validaton report |
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| Full document | emd_48233_full_validation.pdf.gz | 948.5 KB | Display | |
| Data in XML | emd_48233_validation.xml.gz | 22.3 KB | Display | |
| Data in CIF | emd_48233_validation.cif.gz | 29 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-48233 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-48233 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_48233.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.048 Å | ||||||||||||||||||||||||||||||||||||
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Mask #1
| File | emd_48233_msk_1.map | ||||||||||||
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-Half map: #1
| File | emd_48233_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_48233_half_map_2.map | ||||||||||||
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Sample components
-Entire : Phosphatidylinositol-3 kinase class III complex I bound to RAB1A
| Entire | Name: Phosphatidylinositol-3 kinase class III complex I bound to RAB1A |
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| Components |
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-Supramolecule #1: Phosphatidylinositol-3 kinase class III complex I bound to RAB1A
| Supramolecule | Name: Phosphatidylinositol-3 kinase class III complex I bound to RAB1A type: complex / ID: 1 / Parent: 0 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 384.45 KDa |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 Component:
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| Grid | Model: Quantifoil Active R2/1 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY | |||||||||||||||
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Specialist optics | Energy filter - Slit width: 20 eV |
| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 19300 / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 81000 |
| Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
United States, 1 items
Citation















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Processing
FIELD EMISSION GUN

